Vol.16, Suppl.2, 2019-Table of Contents
  • Autodigestion in Physiological Shock, Organ Dysfunction and Death
  • Abstract A longstanding question in research on organ failure after physiological shock (such as trauma, burns, sepsis, surgery and medical emergencies) is the underlying mechanism for a progressive loss of cell and tissue functions. Our systematic analysis of this problem has served to identify digestive enzymes as key players [1, 2]. After synthesis and discharge from the pancreas, the digestive enzymes are usually contained inside the lumen of the small intestine where they break down food every day. Escape of the digestive enzymes out of the lumen of the intestine is kept to a minimum by the mucosal barrier in the… More
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  • Quantifying Heterogeneity of Cell-ECM Interactions Through Integrated Biophysical Analyses
  • Abstract Cell-extracellular matrix (ECM) interactions are critical modulators of repair and regeneration. However, variability within individual cells of the same cell type and within the ECM microenvironment can lead to heterogeneous outcomes that may limit the reliable application of cell-biomaterial constructs in regenerative medicine. Understanding the origins of heterogeneity is critical to overcoming this challenge and requires measurement of cell-ECM interactions at the single cell level. There are four core biophysical modules that cells employ to interact with their surrounding ECM: protrusion, adhesion, contractility, and matrix remodeling. Conventional approaches measure these interactions in separate experiments on separate cells, resulting in bulk… More
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  • Molecular Mechanoimmunology
  • Abstract The immune response is orchestrated by a variety of immune cells. The function of each cell is determined by the collective signals from various immunoreceptors whose expression and activity depend on the developmental stages of the cell and its environmental context. Recent studies have highlighted the presence of mechanical forces on specific immunoreceptor–ligand bonds, which are transmitted across the cell membrane, potentially inducing mechanotransduction. As mechanobiology intersects with immunology, the interest to explore how immune cells sense, respond and adapt to their mechanical environment is rapidly growing. In this talk, I will review recent advances in the emerging field of… More
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  • Immune Cells Migrating through the Brain Endothelia Junctions Served as Shuttles for Nanoparticles Delivery to Glioblastoma
  • Abstract Most cells survive and grow by attaching and spreading on a substrate. They generate internal tension that contracts the cell body and thus exert tractions on the underlying substrate through focal adhesions. Traction force also plays a critical role in many biological processes, such as inflammation, metastasis, and angiogenesis. Thus, measuring the cell traction force provides valuable information on understanding the underlying mechanism of these biological processes. Here, a traction force microscopy (TFM) method using super thin hydrogels composed of immobilized fluorescent beads was utilized to quantify the mechanical forces generated during the transmigration of Jurkat cells (a human T… More
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  • Numerical Simulation of Myocardial Bridging in Patients with Hypertrophic Cardiomyopathy
  • Abstract A myocardial bridge (MB), a congenital anomaly of the coronary artery, occurs when a segment of the epicardial coronary artery goes underneath the myocardium. MBs are often observed in the middle part of the left anterior descending (LAD) artery. MB squeezes the vessel wall periodically and induces hemodynamic abnormalities which are correlated with angina and myocardial ischemia. The level of hemodynamics disturbances induced by MB depends on the myocardial bridge length, the degree of myocardial contractility, thickness, and location [1]. Hypertrophic cardiomyopathy (HCM), characterized by abnormal thickening of the heart wall, is a leading cause of death in patients of… More
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  • An Approach to Medical Device Innovation: Springboard from Dr. Fung’s Biomechanical Foundation
  • Abstract In celebration of Dr. Fung’s 100 birthday, the presentation will focus on a biomechanical design-based approach to innovation of medical devices that addresses unmet clinical needs ranging from cardiovascular diseases (e.g., ischemic heart disease and heart failure) to obesity. The technologies attempt to restore biomechanical homeostasis through a minimally invasive (e.g., percutaneous or laproscopic) approach in time efficient and cost-effective manner. The illustratory technologies include: A) A catheter for selective retroperfusion and “arterialization” of coronary veins for myocardial revascularization; B) A suction-based catheter for ease of trans-septal access; and C) A laproscopic and reversible restrictive device for weight loss without… More
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  • From Cell Mechanobiology to Mechanomedicine: A Research Path Inspired by Fung - Dedicated to Prof. YC Fung on the Occasion of His Centennial Birthday
  • Abstract Decades ago YC Fung proposed that mechanical stress could have substantial impacts on remodeling and growth of living tissues. Fung also proposed the concept of residual stress in blood vessels and quantified residual stress in excised arteries [1]. However, how stress influences cell and tissue functions remains elusive. At the cellular level, we have quantified myosin II mediated pre-existing tensile stress (prestress) in living cells and demonstrated that the prestress (the endogenous cytoskeletal tension) regulates cell stiffness, gene expression, and long-distance stress propagation in the cytoplasm to activate enzymes [2]. The prestress even impacts on force-induced direct chromatin stretching and… More
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  • Multiscale Modeling of Clathrin-Mediated Endocytosis
  • Abstract Endocytosis is the process of uptake of cargo and fluid from the extracellular space to inside the cell; defects in endo- cytosis contribute to a wide spectrum of diseases including cancer, neurodegeneration, and heart disease. Clathrin- mediated endocytosis (CME) is an archetypal example of a membrane deformation process where multiple variables such as pre-existing membrane curvature, membrane bending due to the protein machinery, membrane tension regulation, and actin-mediated forces govern the progression of vesiculation. My group has been working for the past few years on deciphering the biophysical determinants of CME using multiscale modeling. We recently showed that membrane tension… More
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  • Impact of Plaque Erosion on Stress/Strain and Flow Shear Stress Calculation: An OCT-Based FSI Modeling Study
  • Abstract Plaque erosion, one of the primary causes for coronary thrombosis, is responsible for about one third of the patients with acute coronary syndrome (ACS) [1]. Histological studies characterized the eroded plaque as a plaque with following morphological features: 1) plaque intima having direct contact with intraluminal thrombus due to the absence of endothelium or endothelial injury; 2) without rupture in the fibrous cap; 3) abundance of proteoglycans and smooth muscle cells on the luminal surface under the thrombus [2]. These characteristics has been applied in in vivo diagnosis of plaque erosion using optical coherence tomography (OCT) imaging technology and specific… More
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  • Mass Transport of LDL in Stenotic Right Coronary Arteries
  • Abstract The blood flow and mass transport pattern of low-density lipoprotein (LDL) in a right coronary artery with two stenoses are studied. Computations were carried out under physiological conditions. Our results show a strong correlation between wall shear stress (WSS) and distribution patterns of LDL. More
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  • Image-Based Modeling for Atherosclerotic Coronary Plaque Progression and Vulnerability Research
  • Abstract Medical imaging and image-based computational modeling have been used by many researchers in recent years to quantify atherosclerotic plaque morphological and biomechanical characteristics and predict the coronary plaque growth and rupture processes. However, it has been hard to validate model predictions due to imaging resolution limitation, lack of clinical events and plaque rupture data. This article reviews recent advances in coronary plaque research over the past decade, including medical imaging techniques represented by intravascular ultrasound (IVUS) and optical coherence tomography (OCT), computational modeling and their applications in plaque progression and vulnerability analyses and predictions. The clinical application and future development… More
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  • Hydrogels with Enhanced Biomechanical and Mechanobiological Properties
  • Abstract From a mechanical point of view, articular cartilage can be considered as a viscoelastic porous material. Its dissipation capabilities are therefore central for its functional behavior. Based on this observation, we focused our studies of dissipative aspects in cartilage either from a biomechanical or mechanobiological point of view. In particular, we capitalized on the new obtained insight of dissipative behavior or sources in materials for the development of functional biomaterials for cartilage tissue engineering. We pioneered in proposing dissipation as a mechanobiological variable for cartilage tissue engineering [1]. As can be observed on Fig. 1, a correlation exists between the… More
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  • Convolution Neural Networks and Support Vector Machines for Automatic Segmentation of Intracoronary Optical Coherence Tomography
  • Abstract Cardiovascular diseases are closely associated with deteriorating atherosclerotic plaques. Optical coherence tomography (OCT) is a recently developed intravascular imaging technique with high resolution approximately 10 microns and could provide accurate quantification of coronary plaque morphology. However, tissue segmentation of OCT images in clinic is still mainly performed manually by physicians which is time consuming and subjective. To overcome these limitations, two automatic segmentation methods for intracoronary OCT image based on support vector machine (SVM) and convolutional neural network (CNN) were performed to identify the plaque region and characterize plaque components. In vivo IVUS and OCT coronary plaque data from 5… More
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  • Three Dimensional Finite Element Simulation of Atherosclerosis via Morphoelasticity
  • Abstract Atherosclerosis is a disease considered to be one of the leading causes of death. Understanding the behavior and dynamics of the vessel wall before and after atherosclerosis has been a motivation for many studies. We investigate this phenomenon as a combination of mechanical deformation of the vessel wall along with cell and chemical dynamics that occur within. We consider the vessel wall as a growing hyperelastic material with three layers; intima,media and adventitia. Each of these layers have a different set of mechanical properties [1]. To describe tissue growth, we use morphoelasticity as the mathematical framework. The growth tensor in… More
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  • Numerical Analysis of Motion and Stress Distribution of Circulating Tumor Cells in Micro Vessels
  • Abstract The motion of circulating tumor cells (CTCs) in microcirculatory system is one of the critical steps during cancer metastasis. The moving behavior and stress distribution of circulating tumor cells under different geometry and flow conditions are important basis for studying the adhesion between circulating tumor cells and vessel walls. In the present work, the motion and deformation of circulating tumor cells in capillary tubes are numerically studied using the immersed boundary method (IBM). The membrane stress distribution of CTCs in confined tubes are investigated with under vessel diameters, hematocrit (Ht) values and capillary numbers (Ca). The results show that the… More
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  • In Vitro Measurement of Blood Flow in Microvascular Network with Realistic Geometry
  • Abstract We measured a blood flow in a polydimethysiloxane micro channel to reflect the complex geometry of a microvascular network. A flow rate was compared between two working fluids: water and blood. The measured flow rate reflected the bifurcation effects on the apparent viscosity determined by hematocrit, as well as the effects of the surrounding flow channels as bypasses. More
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  • Biomechanical Characteristics Closely Related with Immune Functions of Dendritic Cells
  • Abstract As potent antigen presenting cells, dendritic cells (DCs) are utilized to deliver the signals essential for the initiation of immune responses. The motility of DCs is crucial for migration of immature DCs (imDCs) in peripheral tissue and the interaction between mature DCs (mDCs) and naïve T cells in the secondary lymph node. From biomechanical viewpoint, the deformability of cells is necessary for their motility. Deformation of cells can be divided into active deformation (e.g. chemotaxis) and passive deformation (e.g. migration under shear stress of blood flow). However, there is no detailed study on the deformability of DCs including imDCs and… More
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  • Path Selection of a Spherical Capsule in a Branched Channel
  • Abstract Capsules are liquid droplets enclosed by a thin membrane which can resist shear deformation. They are widely found in nature (e.g. red blood cells) and in numerous applications (e.g. food, cosmetic, biomedical and pharmaceutical industries [1]), where they often flow through a complicated network of tubes or channels: this is the case for RBCs in the human circulation or for artificial capsules flowing through microfluidic devices. Central to these flows is the dynamic motion of capsules at bifurcations, in particular the question of path selection. A good understanding of this problem is indeed needed to elucidate some intriguing phenomena in… More
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  • Comparison of the Virtual Fields Method and the Optimization Method to Characterize Regional Variations in Material Properties of Soft Tissues
  • Abstract Characterizing regional variations of material properties in soft tissues is essential for biomedical engineering and clinical medicine, including but not limited to cancerous disease detection and patient-specific surgical planning of cardiovascular diseases. Identification of nonhomogeneous material property distribution usually requires solving inverse problems in nonlinear elasticity. Generally, inverse algorithms can be categorized into two groups: iterative inversion and direct inversion. In direct inversion, the material property distribution of soft tissues is estimated directly from the equilibrium equations, while the inverse problem is posed as an optimization problem in iterative inversion. In this presentation, we compare the performance of one direct… More
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  • Recovery of 3D Tractions Exerted by Cells on Fibrous Extracellular Matrices
  • Abstract Tractions exerted by cells on the extracellular matrix (ECM) are critical in many important physiological and pathological processes such as embryonic morphogenesis, cell migration, wound healing, and cancer metastasis. Traction Force Microscopy (TFM) is a robust tool to quantify cellular tractions during cell-matrix interactions. It works by measuring the motion of fiducial markers inside the ECM in response to cellular tractions and using this information to infer the traction field. Most applications of this technique have heretofore assumed that the ECM is homogeneous and isotropic [1], although the native ECM is typically composed of fibrous networks, and thus heterogeneous and… More
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  • Mechanics Based Tomography Using Camera Images
  • Abstract It is well known that the mechanical properties of tissues may vary spatially due to changing tissue types or due to inherent tissue disease. For example, the biomechanical properties are known to vary throughout blood vessels [1]. Diseases such as cancers may also lead to locally altered mechanical properties, thus allow a preliminary diagnosis via finger palpation. Quantifying the mechanical property distribution of tissues for a given constitutive equation will allow to characterize the biomechanical response of tissues. This may help to 1) predict disease progression, 2) diagnose diseases that alter the biomechanics of the tissue, e.g., skin cancers, breast… More
  •   Views:1567       Downloads:701        Download PDF
  • Inverse Estimation of 3-D Traction Stress Field of Adhered Cell based on Optimal Control Technique using Image Intensities
  • Abstract Cells adhere to a substrate and generate traction forces in focal adhesions that enable them to apprehend extracellular mechanical properties [1]. Current concerns are focused on mechanisms how the mechanical balances hold in the cell and affect the cell behavior, and therefore non-invasive measurement techniques for the cell traction forces are required. The cell traction force microscopy (TFM) generalized by Dembo and Wang [2] is an attractive approach to non-invasively estimate cell traction force fields, in which an inverse problem is solved using a mechanical model of the substrate and displacement fields from fluorescent images of immersed beads in the… More
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  • Machine Learning Prediction of Tissue Strength and Local Rupture Risk in Ascending Thoracic Aortic Aneurysms
  • Abstract A Multi-layer Perceptron (MLP) neural network model [1] is developed to predict the strength of ascending thoracic aortic aneurysm (ATAA) tissues using tension-strain data and assess local rupture risk. The data were collected through in vitro inflation tests on ATAA samples from 12 patients who underwent surgical intervention [2]. An inverse stress analysis was performed to compute the wall tension at Gauss points. Some of these Gauss points are at or near sites where the samples eventually ruptured, while others are at locations where the tissue remained intact. A total of 27,648 tension- strain curves, including 26,676 2223 nonrupture and… More
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  • On the Identification of Heterogeneous Nonlinear Material Properties of the Aortic Wall from Clinical Gated CT Scans
  • Abstract It is well known that mechanical properties of the aortic wall exhibit patient-specific variations. Recent experimental findings also suggest the aortic wall properties are highly region-specific [1-2]. Thus, in vivo heterogeneous (non-uniform) nonlinear mechanical properties of the aortic wall of individual patients needs to be noninvasively identified for accurate prediction of clinical events (e.g. aortic rupture).
    In this study, we developed an inverse approach for identification of patient-specific non-uniform material properties of the aortic wall from gated 3D CT scans. This inverse approach leverages the fact that the in vivo transmural mean stress (tension) of the aortic wall is… More
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  • Effect of Protein-Induced Membrane Curvature on the Receptor-Ligand Binding Constant
  • Abstract Cell adhesion is a fundamental biological process involved in many crucial cellular activities such as tissue formation, immune response, and cell locomotion [1, 2]. The adhesion process is mediated by the specific binding of membrane-anchored receptor and ligand proteins, which is quantified by the two-dimensional binding equilibrium constant [3-5]. These adhesion proteins are associated with cell membranes either via transmembrane domains or via GPI anchors, and may very likely generate membrane curvature, which has been shown for a number of membrane proteins to play an important role in organelle shaping, vesicle trafficking, cell fusion and division as well as protein… More
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  • Computational Biomechanical Right Ventricle Modeling with Contracting Bands to Improve Ventricle Cardiac Function for Patient with Repaired Tetralogy of Fallot
  • Abstract Computational biomechanical models are widely used in cardiovascular research for better understanding of mechanisms governing disease development, quantitative diagnostic strategies and improved surgical designs with better outcome. Patients with repaired tetralogy of Fallot (TOF) account for the majority of cases with late onset right ventricle (RV) failure. The current surgical approach, which includes pulmonary valve replacement/insertion (PVR), has yielded mixed results. An innovative PVR surgical approach was proposed using active contracting bands to help ventricle to contract and improve RV function measured by ejection fraction [1]. Muscle active contraction caused by sarcomere shortening leads to change of zero-load configurations. In… More
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  • Comparisons of Patient-specific Active and Passive Models for Left Ventricle in Hypertrophic Obstructive Cardiomyopathy
  • Abstract Hypertrophic cardiomyopathy (HCM) occurs in about 1 of every 500 adults in the general population. It has been reported that left ventricular outflow tract obstruction (LVOTO) is observed in 70% patients with HCM. Systolic anterior motion (SAM) of the mitral valve (MV) is the dominant cause of dynamic outflow tract obstruction in most patients with hypertrophic obstructive cardiomyopathy (HOCM). Currently, the hemodynamic mechanisms of SAM remain unclear. In this study, we developed 12 active and corresponding passive models based on 6 patients’ pre- and post-operative ECG-gated cardiac CT images of patients’ LV at the pre-SAM time point (5% RR interval).… More
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  • Computational Modeling of Human Bicuspid Pulmonary Valve Dynamic Deformation in Patients with Tetralogy of Fallot
  • Abstract Pulmonary valve stenosis (PVS) is one common right ventricular outflow tract obstruction problem in patients with tetralogy of Fallot (TOF). Congenital bicuspid pulmonary valve (BPV) is a condition of valvular stenosis, and the occurrence of congenital BPV is often associated with TOF. Dynamic computational models of normal pulmonary root (PR) with tri-leaflet and PR with BPV in patients with TOF were developed to investigate the effect of geometric structure of BPV on valve stress and strain distributions. The pulmonary root geometry included valvular leaflets, sinuses, interleaflet triangles and annulus. Mechanical properties of pulmonary valve leaflet were obtained from biaxial testing… More
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  • Virtual Implantation of Stent-graft by Finite Element Simulation and Its Applications in Endovascular Treatment Planning for B Type Aortic Dissection
  • Abstract Thoracic endovascular aortic repair has been widely applied to treat Stanford Type B aortic dissection. However, retrograde type A dissection can occur as a complication after thoracic endovascular repair for Stanford type B aortic dissection. In order to investigated the possible mechanical reasons of the new entry occurring when stent grafts were implanted into the true lumen of one type B aortic dissection, a framework of virtual implantation of stent-graft by using finite element simulations was developed in this paper. The animal experiments were adopted to verify the finite element simulation of stent-graft implantation. Moreover, the manufactured stent-grafts were implanted… More
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  • Biomechanical Characterization of Mouse Sclera in Myopia
  • Abstract Myopia, or near-sightedness, is a common ocular condition in which the eye elongates excessively. Development of myopia is associated with, and thought to be facilitated by, changes in the biomechanical properties of the sclera (the white part of the eye). We characterized scleral biomechanics in a mouse model of myopia using unconfirmed compression testing and biphasic theory to extract scleral permeability, in- plane scleral tensile modulus, and through-plane scleral compressive modulus. We find that myopia reduces in-plane tensile modulus and permeability, consistent with scleral tissue remodeling. Such biomechanical outcome measures may offer advantages over more traditional assessments of myopia-associated changes… More
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  • Fully-Coupled Fluid-Structure Interaction (FSI) Simulations of Heart Valve-Left Ventricle Dynamics
  • Abstract Fluid–structure interaction (FSI) is a common phenomenon in biological systems. FSI problems of practical interest, such as fish/mammalian swimming, insect/bird flight, and human cardiac blood flow and respiration often involve multiple 3D immersed bodies with complex geometries undergoing very large structural displacements, and inducing very complex flow phenomena. Simulation of heart valve FSI is a technically challenging problem due to the large deformation of the valve leaflets through the cardiac fluid domain in the atrium and ventricular chambers.
    Recently, we developed a FSI computational framework [1] for modeling patient-specific left heart (LH) dynamics using smoothed particle hydrodynamics (SPH) for… More
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  • Sensing Traction Force Induces Cell-Cell Distant Communications for the Rapid Network Assembly of Airway Smooth Muscle Cells
  • Abstract The collective functions at cell population level rely on cell-cell communications with or without direct contacts [1-3]. The long-range biomechanical force propagating across certain scales far beyond single cell size may reserve the capability to trigger coordinative biological responses within cell population [3-5]. Whether and how cells communicate with each other mechanically in a distant manner remains largely to be explored. Airway smooth muscle (ASM) cells are one crucial component in providing mechanical support and contraction force for the bronchial tubes in respiratory system, whereas the mechanical property of ASM is also associated with asthma attack, and during airway hyper-responsiveness,… More
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  • An Isogeometric Analysis Computational Platform for Material Transport Simulation in Complex Neurite Networks
  • Abstract Neurons exhibit remarkably complex geometry in their neurite networks. So far, how materials are transported in the complex geometry for survival and function of neurons remains an unanswered question. Answering this question is fundamental to understanding the physiology and disease of neurons. Here, we have developed an isogeometric analysis (IGA) based platform for material transport simulation in neurite networks. We modeled the transport process by reaction-diffusion-transport equations and represented geometry of the networks using truncated hierarchical tricubic B-splines (THB-spline3D). We solved the Navier-Stokes equations to obtain the velocity field of material transport in the networks. We then solved the transport… More
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  • The Dendritic Cells’ Immunological Behaviors Modulated by the Spatial Confinements of Deposited Fibrin Matrix
  • Abstract The responses of dendritic cells (DCs) to the mechanical microenvironment caused by implanted materials are highly correlated to the host immune responses and largely determines the outcome of tissue regeneration [1,2]. In the early stage of the inflammations following injury or implantation, a large amount of fibrin would deposit around the implanted materials and form a microporous fibrous-liked network structure, which can provide mechanical microenvironment with different spatial confinement in dimensions for following recruited DCs. Herein, we have established a useful model by salmon fibrin to mimic the deposited fibrin matrix and found that DCs cultured on or in fibrin… More
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  • Biophysical Properties and Motility of Human Dendritic Cells Deteriorated by Suppressive Cytokines Through Cytoskeleton Remodeling
  • Abstract Dendritic cells (DCs) play a crucial role in initiating and amplifying both the innate and adaptive immune responses [1]. Clinically, the DCs-based immunotherapy against cancer is considered one of the most promising therapies to overcome cancers, but there are still many challenges need to be overcome [2]. The motility of DCs is especially crucial for migration of immature DCs into peripheral tissue and dynamic physical interaction between mature DCs and naive T cells in the secondary lymph node. This study focuses on the investigations of DCs at different differentiation stages and under various suppressive cytokines (VEGF, TGF-β1 and IL-10) conditioned… More
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  • Mechanosensing Dynmics of Red Blood Cells
  • Abstract Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced Ca2+ influx [1]. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and Ca2+… More
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  • In Vivo Biomechanical Measurements Using Vibrational Optical Coherence Tomography
  • Abstract Vibrational Optical Coherence Tomography (VOCT) is new technique capable of noninvasively and nondestructively measuring the biomechanical properties of tissues in vivo. The technology utilizes audible sound combined with infra-red light applied transversely to the tissue surface to obtain the resonant frequencies of both the cellular and extracellular components of tissue. The measured value of the resonant frequency is related to the elastic modulus and the sample dimensions. The technique is calibrated by making in vitro measurements of the Young’s modulus using uniaxial tensile experiments on the same samples used to make VOCT measurements. In this presentation we describe the details… More
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  • Biomechanical Measurements of Ocular Tissues In Vivo
  • Abstract Vibrational Optical Coherence Tomography (VOCT) is new technique capable of nondestructively measuring the biomechanical properties of ocular tissues in vivo. The technology utilizes audible sound combined with OCT imaging to obtain the resonant frequencies of both the cellular and extracellular components of tissue. The measured value of the resonant frequency is converted into a modulus using the tissue thickness, determined by OCT imaging, and a calibration curve of tissue modulus versus resonant frequency squared divided by sample thickness obtained from in vitro experiments. In this presentation we extend our analysis to ocular tissues specifically the cornea and sclera and discuss… More
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  • In Vivo Biomechanical Measurements of Benign and Cancerous Skin Lesions Using Vibrational Oct
  • Abstract Previous literature reports suggest that tissue stiffness is a predictor of cancer and metastatic behavior of lesions. We have used optical coherence tomography and vibrational analysis (VOCT) to characterize normal skin, scar, a verrucous carcinoma (a squamous cell carcinoma subtype), a basal cell carcinoma and benign skin lesions non-invasively and non-destructively. The results suggest that epidermal thickening and increased keratin and basal cell production occur in malignant lesions and lead to increases in surface hills and valleys as well as subsequent increases in epidermal stiffness values. Increased stiffness of the epidermis is a result of increased keratin and basal cell… More
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  • Finite Element Analysis of 4D Printing
  • Abstract This presentation focuses on the new and upcoming concept of 4D printing and its vast scope and importance in the research and development in industry. The 3D printing object is considered as a layered structure. Each layer may have different orientation. Therefore each layer may behave differently under the change of its environment. We formulate the theoretical shape changing process of 4D printing resulted from (I) the biological growth or swelling, (II) the change of temperature, and (III) the effect of electric field on piezoelectric material of the 3D printing product. Then we illustrate this theory visually through finite element… More
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  • Experimental and Analytical Studies of Tumor Growth
  • Abstract Most biological phenomena commonly involve with mechanics. In this work, we proposed an innovative model that tumor is considered as a pyroelastic medium consisting of two parts: solid and fluid. The variation of solid part depends on whether the drug has been effectively delivered to the tumor site. We derived the governing equations of the tumor, in which large deformation is incorporated. Meanwhile, the finite element equations for coupled displacement field and pressure field are formulated. We proposed two sets of porosity and growth tensor. In both cases the continuum theory and FEM are accompanied by accurate numerical simulations. To… More
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  • Dual 3D Printing Hierarchical Nano/Micro Vascularized Bone Tissue
  • Abstract The vascularization is the most significant to achieve efficient supplement of the nutrients and oxygen for tissue and organ regeneration. However, there is a remaining challenge to fabricate a durable and functional vascularized tissue. Currently, 3D printing has emerged as a promising technique to fabricate vascular networks in many studies due to its superior controllability, reproducibility, and repeatability. In the current study, the main objective is to utilize an advanced dual 3D printing technique including stereolithography (SLA) and fused deposition modeling (FDM) to create a biomimetic bone tissue with perfusable vascular networks. Specifically, the vascularized bone construct was fabricated by… More
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  • LOX Alleviates Rat Intervertebral Disc Degeneration Through ECM Improvement and Anti-Apoptotic Protection in Nucleus Pulposus Cells
  • Abstract This study was focus on the exploring the therapeutic function of lysyl oxidase (LOX) in rat nucleus pulposus (NP) cells in intervertebral disc degeneration (IVDD). To do this, a Sprague-Dawley (SD) rat caudal spine degeneration model was established by puncturing the Co5-6 disc. NP cells apoptosis and extracellular matrix (ECM) degeneration in IVDD were evaluated by real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR), Hematoxylin-Eosin (H&E) and immunofluorescence. Then, the therapeutic effect of LOX on IVDD was evaluated by histological staining. In vitro, the regulator effect of LOX on degenerate rat NP cell was explored. ECM relate proteins and cytokines were… More
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  • Macrophages as A Mechano-Transducer to Direct the Osteogenic Differentiation of Mesenchymal Stem Cells
  • Abstract It has been widely recognized that stem cells possess the potential of osteogenic differentiation, which greatly contribute to bone repair. Recently, accumulating evidences have indicated that mechanical cues are required for bone repair [1,2]. However, how local and recruited stem cells in the bone architecture receive the mechanical signals is poorly understood [3,4]. The purpose of this study is to demonstrate that macrophages potentially transduce the mechanical signals for stem cell osteogenic lineage. This demonstration has been carried out through a co-culture system to investigate the effect of macrophages which subjected to cyclic stretch on the osteogenic potential of bone… More
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  • Molecular and Cellular Immuno-Engineering
  • Abstract Genetically-encoded biosensors based on fluorescence proteins (FPs) and fluorescence resonance energy transfer (FRET) have enabled the specific targeting and visualization of signaling events in live cells with high spatiotemporal resolutions. Single-molecule FRET biosensors have been successfully developed to monitor the activity of variety of signaling molecules, including tyrosine/serine/threonine kinases. We have a developed a general high-throughput screening (HTS) method based on directed evolution to develop sensitive and specific FRET biosensors. We have first applied a yeast library and screened for a mutated binding domain for phosphorylated peptide sequence. When this mutated binding domain and the peptide sequence are connected by… More
  •   Views:2146       Downloads:663        Download PDF
  • Differential Organization of Airway Smooth Muscle Cells on Tubular Surface as A Novel Mechanobiology Mechanism of Airway Tissue Morphogenesis
  • Abstract Airway smooth muscle cells (ASMCs) exists within the bronchial airway wall in a form of spirally winding bundles [1]. This pattern emerges early during embryonic development and is involved in airway branching [2], providing the airway appropriate contractile capacity and resistance to circumferential tension in health or causing excessive airway narrowing in disease such as asthma. Despite its importance, the cause of ASMCs self-organization remains largely a mystery. Previously, we have demonstrated in 2D that ASMCs can sense the curvature in their microenvironment and change behaviors in differentiation, orientation and migration accordingly [3]. Here we further explore in 3D microenvironment… More
  •   Views:1611       Downloads:683        Download PDF
  • Dependency of Nuclear Deformation of Smooth Muscle Cells on Tissue Stretch Direction May Explain Anisotropic Response of Aortic Wall to Hypertension
  • Abstract Aortic wall thickens in response to hypertension. Many studies reported that the wall thickening occurs to maintain the wall stress in the circumferential direction at a constant level. In case of the longitudinal direction, however, there are few studies suggesting the constancy of the stress. Such anisotropic response may be attributable to the circumferential alignment of the smooth muscle cells (SMCs) in the wall [1]. However, to the authors’ knowledge, there are no study discussing the underlying mechanism of the anisotropic response. It has been reported that mechanical deformation of the nuclei causes transcription upregulation [2]. This might suggest that… More
  •   Views:2255       Downloads:643        Download PDF
  • Engineering Zap70 Biosensor Through Directed Evolution for Applications in Single-Cell Imaging and Immunotherapy
  • Abstract Genetically-encoded biosensors based on Fluorescence Resonance Energy Transfer (FRET biosensors) have been widely used to dynamically track the activity of Protein Tyrosine Kinases (PTKs) in living cells because of their sensitive ratiometric fluorescence readout, high spatiotemporal resolution. However, the limitation in sensitivity, specificity, and dynamic range of these biosensors have hindered their broader applications, and there was a lack of efficient ways to optimize FRET biosensors. Here we established a rapid, systematic and universal approach for FRET biosensor optimization through directed evolution which involves generating genetic diversity and screening for protein variants with desired properties at the same time and… More
  •   Views:4444       Downloads:1571        Download PDF
  • Histone Modification and Chromatin Reorganization Regulated by Mechanical Tension in Single Cell Mitosis
  • Abstract The dramatic re-organization of chromatin during mitosis is perhaps one of the most fundamental of all cell processes [1,2]. It remains unclear how epigenetic histone modifications, despite their crucial roles in regulating chromatin architectures, are dynamically coordinated with chromatin reorganization in controlling this process. Mechanical cues have also been shown to play important roles in modulating gene expressions and cellular functions [3,4]; however, it is still unclear about the mechanical regulations of epigenetics and chromatin organization. In this study, we have developed and characterized biosensors with high sensitivity and specificity based on fluorescence resonance energy transfer (FRET). These biosensors were… More
  •   Views:1819       Downloads:648        Download PDF
  • On the Onset of Cracks in Arteries
  • Abstract We present a theoretical approach to study the onset of failure localization into cracks in arterial wall. The arterial wall is a soft composite comprising hydrated ground matrix of proteoglycans reinforced by spatially dispersed elastin and collagen fibers. As any material, the arterial tissue cannot accumulate and dissipate strain energy beyond a critical value. This critical value is enforced in the constitutive theory via energy limiters. The limiters automatically bound reachable stresses and allow examining the mathematical condition of strong ellipticity. Loss of the strong ellipticity physically means inability of material to propagate superimposed waves. The waves cannot propagate because… More
  •   Views:1752       Downloads:641        Download PDF
  • Modeling Mechano-chemical Couplings in Bone Adaptation by Remodeling
  • Abstract Bone adaptation by remodeling is a process to change its outer shape and internal structure to the changing mechanical environment by osteoclastic bone resorption and osteoblastic bone formation. These cellular activities are regulated by mechanosensory network of osteocytes embedded in bone matrix. An imbalance between bone resorption and formation due to low loadings or disuse results in metabolic bone disorders such as osteoporosis. Many studies have identified various signaling pathways that regulate these cellular activities; however, the physiological and pathological conditions of bone as a system remain difficult to understand because of the complexity of the signaling networks including mechano-biochemical… More
  •   Views:2187       Downloads:756        Download PDF
  • Dynamics of Trabecular Meshwork Deformation under Pulsatile Intraocular Pressure
  • Abstract Elevated intraocular pressure (IOP) is the most important risk factor for disease progression in glaucoma patients. The elevation is predominantly due to the increase in the aqueous outflow resistance in the trabecular outflow pathway. Recent data have shown that the resistance increase is correlated with changes in the tissue stiffness. To this end, we developed a mathematical model to simulate how the tissue stiffness can affect the deformation of the trabecular meshwork (TM) that can be determined experimentally. The goal of the study is to develop a method to non-invasively determine the TM stiffness in patients through measurement of the… More
  •   Views:1781       Downloads:656        Download PDF
  • Kinematic and Dynamic Characteristics of Pulsating Flow in 180° Tube
  • Abstract Pulsating flow in a human aortic arch is studied from its kinematic and dynamic characteristics of transient tubular boundary layer. The results can only be obtained by a 3D fluid dynamic (CFD) analysis for the rapidly accelerated and decelerated systolic flow. The flow is based on a prescribed inlet velocity, VO(t), which can be expressed as the instantaneous Reynolds number, Re(t) = ρDVO/μ in which D is the tube diameter, ρ the blood density and μ the dynamic viscosity. Computation of pressure field requires a reference pressure at the downstream end section. The pressure is based on the pulse in… More
  •   Views:2339       Downloads:665        Download PDF
  • Mechanical Relaxation during Cell Reprogramming
  • Abstract Cell reprograming technologies have broad applications in cell therapy, disease modeling and drug screening. Direct reprogramming of fibroblasts into induced neuronal (iN) cells has been achieved via the forced expression of three transcription factors: Ascl1, Brn2 and Myt1l. Accumulative evidence suggests that biophysical factors in the microenvironment can regulate the epigenetic state and cell reprogramming. However, whether intracellular mechanical properties regulate cell reprogramming remains unknown. Here, we show for the first time, that the mechanical property of cells is modulated during the early phase of reprogramming as determined by atomic force microscopy (AFM) and high-throughput quantitative deformability cytometry (q-DC). We… More
  •   Views:1631       Downloads:660        Download PDF
  • Identification of Lysyl Oxidase on Repression of Inflammation for Promoting Anterior Cruciate Ligament Remodeling
  • Abstract At present, anterior cruciate ligament (ACL) damage repair is still a huge challenge. Our previous studies indicated that the Lysyl oxidase (LOX) were significantly reduced in injurious ACL fibroblasts, which is the major reason for its poor healing ability. The main purpose of our study was to detected the potential of LOX to act as an anabolic agent in injured ACL. The effect of LOX on the ACL at a concentration of 20ng/mL was investigated. The molecular mechanisms and signaling pathway were elucidated by RNA-sequencing, q-PCR and western blotting. For the in vivo study, the LOX was injected into the… More
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  • hnRNPK a Possible Mechanosensitive Gene: Its Function in Chondrocytes and Osteoarthritis
  • Abstract Mechanical stimulation contributes to the development, homeostasis, integrity and functionality of the articular cartilage by modulating several cellular activities including production and remodeling of extracellular matrix (ECM), chondrocyte differentiation, proliferation and apoptosis. On the other hand, abnormal mechanical strain play a critical role in osteoarthritis (OA) pathogenesis by inducing ECM degradation and chondrocyte apoptosis. Furthermore, deleterious mechanical loading can also stimulates the production of pro-inflammatory mediators such as interleukin 1β (IL-1β) that promote to cartilage degradation, chondrocyte hypertrophy and inflammation [1]. Heterogeneous nuclear ribonucleoprotein K (hnRNPK), a member of the hnRNP family, is implicated in the expression, stabilization and organization… More
  •   Views:2044       Downloads:753        Download PDF
  • Role of NFAT5 in Hypertonic Stress-Induced Atherosclerosis in Endothelium
  • Abstract Globally, consumption of sodium (5.8 g per day) was far above the optimal levels (2.3 g per day). High intake of sodium was the leading dietary risk factor for deaths, which caused by cardiovascular disease [1]. Nevertheless, how high-salt intake leads to the occurrence of many cardiovascular diseases such as atherosclerosis is still not very clear. Dmitrieva has reported that elevated sodium concentration promoted thrombogenesis by activating the signal pathway of NFAT5 (nuclear factor of activated T cells 5), a transcription factor which orchestrates cellular defense against osmotic stress [2]. Inflammatory is accompanied with the entire development process of atherosclerosis.… More
  •   Views:2156       Downloads:707        Download PDF
  • Diabetes and Thrombosis: The Dark Side of the Force
  • Abstract Thrombotic diseases where platelets form clots and obstruct blood vessels remains the leading cause of death and disability in the world. Despite intense investigation over the last 40 years into the discovery and development of more effective drugs, less than 1 in 6 patients taking anti-thrombotic therapies avoid a fatal event. This situation is likely to worsen in younger generations due to the rapidly growing incidence of diabetes, which makes people more prone to thrombosis and resistant to existing anti-thrombotics with unknown reasons.
    To investigate this, I have developed the ‘Biomembrane Force Probe’ as the first-of-its-kind. This nanotool represents… More
  •   Views:1865       Downloads:657        Download PDF
  • Fast Force Loading Disrupts Molecular Bond Stability in Human and Mouse Cell Adhesions
  • Abstract Force-mediated molecular binding initiates numerous cellular activities such as cell adhesion, migration, and activation. Dynamic force spectroscopy (DFS) is widely used to examine molecular binding and cell mechano-signaling [1]. The rate of dissociation, off-rate, is an important attribute of molecular binding that reflects bond stability. Extensive DFS works have demonstrated that off-rates are a function of force magnitude, yielding signature bond behaviors like “catch bond” [2]. However, as a controversial topic of the field, different DFS assays, i.e., force-clamp and force-ramp assays, often yielded distinctive "off-rate vs. force" relations from the same molecular system [3]. Such discrepancies cast doubt on… More
  •   Views:1609       Downloads:687        Download PDF
  • Atypical Activation of Endogenous Piezo1 Channels by Shear Stress in Endothelial Cells
  • Abstract The sensing of blood flow-evoked shear stress is critical in vascular development and maintenance of a healthy vasculature in the adult [1,2]. The identity of molecules which sense and transduce this force into appropriate vascular anatomy and function is therefore keenly sought. A central question is whether there is a force sensor protein (“receptor”) which directly detects the force, acting either alone or in complex with other proteins. Piezo1 channels are Ca2+-permeable non-selective cationic channels which are activated by membrane stretch. These channels are important for shear stress-sensing and vascular function in embryonic and adult mice. Through whole-cell perforated patch… More
  •   Views:2963       Downloads:704        Download PDF
  • The Effect of Cellular Shape on Differentiation of Dental Pulp Stem Cells
  • Abstract Many studies have shown that cell shape effects cell chromatin aggregation, gene expression, protein synthesis, cell growth, apoptosis, and cytoskeletal rearrangement [1, 2]. Dental pulp stem cells (DPSCs) are capable of osteogenic, dentinogenic, chondrogenic, and neurogenic differentiation. They are regarded as a promising candidate for tissue regeneration. How the cell shape regulates their cell behavior is still unknown. We used micropatterning technology to design single cell patterns in a 1:1, 1:2, 1:4, 1:8, 1:16 length-width ratio of rectangles with the same area. The results indicated that cell shape rearranged the cytoskeleton of DPSCs. The nuclear shape also affected by different… More
  •   Views:2107       Downloads:694        Download PDF
  • The Effect of Short-and Long-Term Simulated Microgravity on Immune Cells
  • Abstract Long-term space flight will be a major mission for International Space Administration. However, it has been shown that exposure to space flight result in immune system dysfunction. Therefore, understand the mechanism of immune response under microgravity condition is a key topic. Macrophage is one of the most important immune cells in human body, playing key roles in both innate and adaptive immune systems. In this research, we used mouse macrophages (RAW264.7) and collected samples at short-term (8 hour), mediate-term (24 hour) and long-term (48 hour) microgravity treatment. We measured cell proliferation, phagocytosis function and used next-generation sequencing (NGS) to obtain… More
  •   Views:2169       Downloads:661        Download PDF
  • Contour-Based Data Analysis: Loading Rate Dependence in Dynamic Catch of Integrin-Ligand Bonds
  • Abstract Cell-matrix interactions guide various cell behaviors, including proliferation, differentiation, migration, etc. Integrins, as a known transmembrane mechanosensor, undergo conformational changes in response to mechanical stimuli, and manipulate cell-matrix chemical-mechanical coupled signaling transduction [1]. The integrin-ligand bond kinetics has gain increasing attention among researchers. Independent studies showed that the integrin-ligand bond has been reported to be reinforced by the applied force f, while the loading rate df/dt had little effect on the bond lifetime [2].
    We previously observed a dramatic increase in bond lifetime beyond a loading rate threshold for the integrin α2β1-DGEA bond, by introducing AFM (Atomic Force Microscopy)… More
  •   Views:1760       Downloads:662        Download PDF
  • From Biomechanics to Molecular Affinity to Systems Immunology – My Path in Biomedical Engineering That is Inspired by Dr. YC Fung
  • Abstract Force is not only involved in motion, but also involved in molecular interactions that guide cells to execute important physiological functions. Getting to know Dr. Fung at an early age shaped my college major decision, which lead me into the field of biomedical engineering. Applying a force-based measurement tool to study T cell receptor interaction with ligands in graduate school prepared me to use technology development as a foundation to answer important biological and clinical questions.
    By combining engineering principle, quantitative modeling, and a deep understanding of biology and medicine, my current research focuses in systems immunology and immune… More
  •   Views:1592       Downloads:641        Download PDF
  • The Dependence of Diffusio-Phoretic Mobility and Aggregation Properties of Proteins on Intermolecular Interaction in Confined System
  • Abstract Phoretic flow can be generated by different types of gradient (e.g. temperature, concentration, or charge gradient) [1-3]. Within micro-to-nano confined system, the diffusio-phoretic property for proteins differs dramatically from that obtained in bulk condition, due to concentration fluctuation that emerges at microscopic level induced by specific and nonspecific interactions between protein and co-solute [4-5]. The phoretic mobility of protein individuals and complex in solute gradients can be theoretically described by continuum model [1-2] that neglects microscopic heterogeneity and determined experimentally by microfluidics [6], but the underlying mechanism of diffusio-phoretic motion for confined protein still remains unclear.
    Our approach to… More
  •   Views:2781       Downloads:692        Download PDF
  • Mapping Single Platelet Forces Directly by Fluorescence Imaging
  • Abstract Platelets are important blood cells mediating hemostasis and thrombosis. Integrin tension plays a critical role in most platelet functions, such as adhesion, activation, aggregation and contraction. Visualizing and measuring single platelet forces are desired in both research and diagnosis of platelet functions. Here we developed integrative tension sensor (ITS) which converts integrin molecular tension to fluorescent signal, therefore enabling cellular force mapping directly by fluorescence imaging. With the ITS, we mapped integrin-transmitted platelet force at 0.4 µm resolution during platelet adhesion and contraction. We found that platelet force distribution has strong polarization which is sensitive to treatment with anti-platelet drugs,… More
  •   Views:2729       Downloads:674        Download PDF
  • Extracellular Matrix Elasticity Gives Integrin a Sweet Change via a p53/miRNA-532/atp2c1 Axis
  • Abstract Extracellular matrix (ECM) elasticity affects the function of a variety of cells. Integrins are transmembrane receptors that considered to be a sensor of cellular mechanical stimulation. The activity of integrins is strongly influenced by glycans through glycosylation events and the establishment of glycan-mediated interactions. Our study found that the level of β1 integrin N-linked glycosylation was significantly down-regulated on softer ECM. Further, sialic acid is a common monosaccharide modified at the end of the sugar chain during N-glycosylation. We subjected the enriched sialylated glycoproteins to gel-based proteomic identification by tandem mass spectrometry and found that the chondrocytes seeded on stiff… More
  •   Views:1656       Downloads:689        Download PDF
  • Ultra-stable Biomembrane Force Probe to Characterize Strong Protein-Protein Interactions on a Living Cell
  • Abstract Biomembrane force probe (BFP) is a single-molecule biomechanical technique that has been widely used to characterize protein dynamics (e.g., protein-protein interactions and protein conformational changes), especially suitable for measuring force-regulated receptor-ligand binding kinetics in situ[1-4]. Integrated with various force spectroscopies, such as lifetime assay, it has become a powerful platform to systematically characterize many force-regulated receptor-ligand dissociation of great biological significance, which cannot be done with traditional solution based assays (e.g., surface plasma resonance) [5].
    Even though the BFP has been quite successful in characterizing binding kinetics of weak and transient molecular interactions, it is still incapable of stably… More
  •   Views:1608       Downloads:654        Download PDF
  • Magnetic Resonance Image-Based Modeling for Neurosurgical Interventions
  • Abstract Surgeries such as implantation of deep brain stimulation devices require accurate placement of devices within the brain. Because placement affects performance, image guidance and robotic assistance techniques have been widely adopted. These methods require accurate prediction of brain deformation during and following implantation. In this study, a magnetic resonance (MR) image-based finite element (FE) model was proposed by using a coupled Eulerian-Lagrangian method. Anatomical accuracy was achieved by mapping image voxels directly to the volumetric mesh space. The potential utility was demonstrated by evaluating the effect of different surgical approaches on the deformation of the corpus callosum (CC) region. The… More
  •   Views:1693       Downloads:667        Download PDF
  • Finite Element Modelling Predicts Large Accommodation Induced Optic Nerve Head Deformations
  • Abstract Accommodation is the ability of the eye to adjust its lens thickness to alter the refractive power through the contraction of ciliary muscles. The loss of accommodation ability due to aging leads to presbyopia, a condition in which the eye is unable to focus on near objects. Glaucoma is a disease that vision is impaired due to damage of the retinal ganglion cell at the optic nerve head (ONH) region, which is the leading cause of irreversible blindness worldwide. The biomechanical theory of glaucoma suggests that the deformations of ONH tissues could (directly or indirectly) drive retinal ganglion cell death.… More
  •   Views:4552       Downloads:1639        Download PDF
  • Effects of Muscle Fatigue on the Kinect Control of Free Throw in the Wheelchair Basketball Sport
  • Abstract Wheelchair basketball is mainly designed for people who are physically challenged with permanent lower body disabilities. Free throw execution is one of the basic skills and could represent the preferred shooting mechanics so as to examine the overall shooting mechanics in basketball players. It requires the body to act as a kinetic chain to summate energy from the wheelchair to the upper extremity for the coordinated movements. Researchers have shown that the kinetic chain of the wheelchair basketball athletes could be affected by the kinematic parameters such as the release velocity and shooting angle [1-3]. The goal of this study… More
  •   Views:2375       Downloads:759        Download PDF
  • Effect of Icariin on Osteoarthritis Fibroblast-Like Synoviocytes: An In Vitro Study
  • Abstract Osteoarthritis (OA) is a chronic joint bone disease which always leads to the dysfunction and disability of arthritis. Synovial inflammation plays an important role in the pathogenesis and progress of OA which can secrete large amounts of inflammatory cytokines. There is an urgent need to find safe and effective drugs that can reduce the inflammation and regulate the pathogenesis of cytokines of the OA disease. Icariin, a traditional Chinese herbal medicine, is the major pharmacological active component of herb Epimedium. This study we investigated the influence of icariin on the main cells in synovium-osteoarthritis fibroblast-like synoviocytes (OA-FLSs). The OA-FLSs were… More
  •   Views:1999       Downloads:750        Download PDF
  • Identification of Btg2 As A Mechanosensitive Gene by Functional Screening Integrative Analyses
  • Abstract Osteoarthritis (OA), with its high disability and mortality rate, is the most common arthritis throughout the world [1]. Exposure of articular cartilage to excessive mechanical stress is deeply involved in the pathogenesis of osteoarthritis (OA) [2,3]. However, the mechanism of how mechanical stress causes cartilage degradation is not clear yet. Here we report that bioinformatics-based integrative analyses can assist in the study of mechanisms modulated by mechanical stress within OA pathology, and we reveal that B-cell Translocation Gene 2 (BTG2) can be a mechanosensitive gene involved in OA development. We obtained OA-associated differentially expressed genes from human and rat datasets… More
  •   Views:2234       Downloads:781        Download PDF
  • Assessment of the Locomotion and the Long-term Efficacy of Biomechanics Foot Orthotic for the Subjects with Adolescent Idiopathic Scoliosis
  • Abstract Scoliosis is the most common type of spinal deformity of the young adults, and women outnumber men about 10:1 [1], in which the Adolescent Idiopathic Scoliosis (AIS) is up to 90% for ages 10 to 16year-old teenagers [2]. Studies revealed that due to the 3-dimensional musculoskeletal deformities, the AIS subjects to the dynamic postural instability including vestibular and proprioception disorders [3-5]. Dynamic postural Balance is monitored by integration of cortical modulation and somatosensory response [6], and the either motor or sensory impairment lead to balance dysfunction as well as pathologic gait. Studies revealed that the biomechanics functional foot orthotics can… More
  •   Views:2394       Downloads:724        Download PDF
  • Multifrequency Microwave Imaging for Brain Stroke Detection
  • Abstract Early diagnosis of stroke with timely treatment could reduce adult permanent disability significantly [1]. Conventional medical imaging tools such as X-ray, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have been widely used for diagnosis of brain disease. However, each of these methods has some limitations. X-ray imaging produces harmful radiation to the human body and challenging to identify early-stage abnormal tissue due to the relatively small dielectric proprieties contrast between the healthy tissue and abnormal tissue at X-ray frequencies [2]. PET provides useful information about soft tissues, but it is expensive and produces poor… More
  •   Views:4404       Downloads:1584        Download PDF
  • Quantitative Method for Biomechanical Evaluation of Bedding Comfortableness
  • Abstract Comfortable bedding is usually designed subjectively because of the difficulty in performing a quantitative evaluation. This paper proposes a quantitative evaluation method of comfortableness of beddings. The bedding shape determining how comfortable an individual may feel in using it depends on the body shape and normal posture of individuals. The internal physical load is expected to relate to the comfortableness of bedding. However, only a few quantitative discussions exist on the relation between the comfortableness of bedding and physical load. This study proposes a new evaluation method of physical load in a relaxed posture. The strain energy of muscles and… More
  •   Views:1699       Downloads:713        Download PDF
  • Matrix Stiffness Promotes Hepatoma Cell Glycolysis and Migration Through YAP-Mediated Mechanotransduction
  • Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal malignancies worldwide. Increased matrix stiffness of extracellular matrix (ECM) is commonly associated with HCC. During tumour formation and expansion, increasing glucose metabolism is necessary for unrestricted growth of tumour cells. Yet, the correlation between matrix stiffness and glucose metabolism in the development of HCC remains unknown. In this study, we aim to investigate the effect of matrix stiffness on glucose metabolism and migration of MHCC97L and HepG2 hepatoma cells, and explore the mechanotransduction involved in this process. Polyacrylamide hydrogels with stiffness gradients of 6, 25, 54 kPa were produced… More
  •   Views:1738       Downloads:696        Download PDF
  • Effects of Three-Dimensional Stiffness on the Proliferation, Stemness And Invasion of Hepatic Cancer Stem Cells
  • Abstract Hepatocellular carcinoma (HCC) is the third most common cancer in the world. Previous studies have shown that hard matrix promotes the proliferation of liver tumor cells. However, the role of matrix stiffness on hepatic cancer stem cells (HCSCs) is still unclear. Three-dimensional hydrogels with different stiffness were used to mimic the normal liver tissue (4kPa) and cancerous liver tissue (26kPa) stiffness. The proliferation, stemness and invasion properties of HCSCs under 3D different stiffness were detected. METHOD: HSCSs were screened and cultured by enrichment method, and the effect of matrix stiffness on HCSCs was studied by three-dimensional culture of HCSCs in… More
  •   Views:1871       Downloads:731        Download PDF
  • Gene Expression Profiling of Human Hepatocytes Grown on Differing Substrate Stiffness
  • Abstract Objective: To study the effects of different substrate stiffness on human hepatocytes using RNA sequencing (RNA-Seq) technology. The stiffness was corresponding to physiology and pathology stiffness of liver tissues.
    Results: With the aid of RNA-Seq technology, our study characterizes the transcriptome of hepatocytes cultured on soft, moderate, stiff and plastic substrates. Compared to soft substrate, our RNA-Seq results revealed 1131 genes that were up-regulated and 2534 that were down-regulated on moderate substrate, 1370 genes that were up-regulated and 2677 down-regulated genes on stiff substrate. Functional enrichment analysis indicated that differentially expressed genes were associated with the regulation of actin… More
  •   Views:1830       Downloads:755        Download PDF
  • The Importance of Niches-Dimensionality in Regulating the Bone Marrow Hematopoietic Stem Progenitor Cells Pool
  • Abstract Research in stem cell biology relies on the knowledge of the cell microenvironment in vivo, known as “stem cell niche”, where stem cells are nurtured by the niche signals. Hematopoietic stem cells (HSCs) are capable of continuously generating and maintaining the body’s full immune and hematopoietic systems. In adult, a pool of hematopoietic cells, including HSCs, primarily reside in the bone marrow (BM) niches that plays critical roles on cell fate. Niche supporting cells, cytokines, extracellular matrix proteins and other biochemical cues associated with HSCs behaviors (quiescence, self-renewal, proliferation, differentiation, mobilization, homing, and apoptosis) has been revealed in quantity. Recently… More
  •   Views:1910       Downloads:761        Download PDF
  • Mechano-Electric Feedback and Arrhythmogenic Current Generation in A Computational Model of Coupled Myocytes
  • Abstract Heterogeneous mechanical dyskinesis has been implicated in arrhythmogenic phenotypes. Strain-induced perturbations to cardiomyocyte electrophysiology (EP) may trigger arrhythmias via a variety of mechano-electric feedback (MEF) mechanisms. While the role of stretch-activated ionic currents (SACs) has been investigated intensively using computational models, experimental studies have shown that mechanical strain can also trigger intra- and inter-cellular calcium waves. To investigate whether the inherent strain dependence of myofilament calcium affinity may promote arrhythmogenic intra- and inter-cellular calcium waves under conditions of pathologic mechanical heterogeneity, we coupled a mathematical model of excitation-contraction coupling (ECC) in rabbit ventricular myocytes to a model of myofilament activation… More
  •   Views:4369       Downloads:1508        Download PDF
  • Recent Progress in Medical Biomaterials
  • Abstract Guided tissue regeneration (GTR) is a technique that selectively guides cells to attach and proliferate towards an injured site to achieve tissue regeneration through a physical barrier membrane. In this review, we presented a brief overview of the development of GTR technology and GTR materials. Nowadays, new technologies such as electrospinning, nanotechnology, controlled release technique, and 3D printing have been introduced into the study of GTR materials. Resorbable membrane as GTR materials are available as alternatives to conventional non-resorbable membranes. Current GTR materials not only act as a physical barrier membrane but also as a scaffold to play a role… More
  •   Views:1689       Downloads:742        Download PDF
  • Mechano Growth Factor (MGF) Expression and Response to Multiple-Mechanical Stimulation after Biodegradable Stent Implantation
  • Abstract Stent implantation is the most effective method in the treatment of cardiovascular disease which always destroy the integrity of the vascular endothelium and the local mechanical environment at the stent segment was changed, especially the biodegradable stents [1]. In this study, 3D printed biodegradable poly (L-lactic acid) stents were implanted into SD rat abdominal aorta and the endothelialization, intimal hyperplasia, and MGF after stent implantation were studied. Besides, based on the MGF we explored the effects of mechanical stimulation on MGF express in vascular endothelial cells and smooth muscle cells, and also the effects of MGF with different concentrations on… More
  •   Views:1667       Downloads:679        Download PDF
  • Expression of Endothelial Tight Junction Protein Occludin under Mechanical Factors after Stent Implantation
  • Abstract Tight junctions are the most apical intercellular junctions of the lateral membrane in endothelial cells, regulating the paracellular material and energy exchange and maintain plasma membrane polarity. Occludin protein is one of the important proteins involved in endothelial tight junctions, and also closely related to the occurrence of atherosclerosis. Therefore, the study of occludin is valuable [1]. With the implantation of coronary stents, the integrity of the vascular endothelium is damaged and the local mechanical environment at the stent segment was changed [2]. The present study tried to explore the impact of mechanical stimulation after stent implantation on the expression… More
  •   Views:2292       Downloads:778        Download PDF
  • Endothelial Tight Junction Protein ZO-1 Response to Multiple-Mechanical Stimulations After Stent Implamtation
  • Abstract Zonula occludens-1 (ZO-1) is a peripheral membrane protein belongs to the family of zona occludens proteins and plays an important role as a scaffold protein which cross-links and anchors tight junction (TJ) strand proteins, within the lipid bilayer, to the actin cytoskeleton[1-2]. Stent implantation is the most effective method in the treatment of cardiovascular disease which always destroy junctions of endothelial cells, the functions of the tight junction were also affected. However, the role of ZO-1 before and after stent implantation has not been fully understood. In this study, the expression of ZO-1 were analyzed by qPCR, western blot and… More
  •   Views:3119       Downloads:811        Download PDF
  • Oscillatory Shear Stress Induces Endothelial Dysfunction through the Activation of P2Y12
  • Abstract Endothelial cell injured or dysfunction, which results lipid deposition and inflammation, is the key point to exacerbate the process of atherosclerosis [1, 2]. Meanwhile oscillatory shear stress is a key factor that results cell dysfunction in vascular disease [3, 4]. Previous research reported that P2Y12 plays a critical role in the development of atherosclerotic lesion through promoting smooth muscle cells migration [5]. As well P2Y12 stimulated the internalization and transendothelial transport of high density lipid. However, whether the P2Y12 induce atherosclerosis through endothelial cell remain elusive. In this study we firstly found P2Y12 were expressed in endothelial cells of atheroprone… More
  •   Views:2188       Downloads:794        Download PDF
  • A New Mass Effect Research Rat Model to Explore the Occuping Effect on Secondary Brain Injuries after ICH
  • Abstract The mechanical response of brain tissue closely relates to cerebral blood flow and brain diseases. During intracerebral haemorrhage (ICH), a mass effect occurs during the initial bleeding. As the hematoma increases, the haematoma mass effect continues to squeeze the brain tissue mechanically, which can even lead to the formation of fatal cerebral hernia. However, fewer studies have focused on the brain damage mechanisms and treatment approaches associated with mass effects compared to the secondary brain injuries after ICH, which may be a result of the absence of acceptable animal models mimicking a mass effect. Thus, a thermo-sensitive poly (N-isopropylacrylamide) (PNIPAM)… More
  •   Views:1675       Downloads:727        Download PDF
  • The Rate of Fluid Shear Stress is a Potent Regulator for Lineage Commitment of Mesenchymal Stem Cells Through Modulating [Ca2+]i, F-actin and Lamin A
  • Abstract Mesenchymal Stem Cells (MSCs) are recruited to the musculoskeletal system following trauma [1] or chemicals stimulation [2]. The regulation of their differentiation into either bone or cartilage cells is a key question. The fluid shear stress (FSS) is of pivotal importance to the development, function and even the repair of all tissues in the musculoskeletal system [3]. We previously found that MSCs are sensitive enough to distinguish a slight change of FSS stimulation during their differentiation commitment to bone or cartilage cells, and the internal mechanisms. In detail, MSCs were exposed to laminar FSS linearly increased from 0 to 10… More
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  • The Mechanical Mechanism of Cortical Folding on 3D Cerebral Organoids
  • Abstract An expansion of the cerebral neocortex is thought to be the foundation for the unique intellectual abilities of humans. The cortical folding has been implicated in neurodevelopmental disorders and yet its origins remain unknown. In vitro culture of 3D cerebral organoids from human pluripotent stem cells has been used to study the fundamental mechanisms of mammalian neurodevelopment and characteristics of human brain development. Here, we explores the mechanism of boundary limitation on the formation of gyri and sulci through the self-organization of human brain organoids. The structure of cerebral organoids was analyzed by morphology observation, pathology and immunofluorescence. The different… More
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  • Microspheres Modified with the Heparin Increasing the Length of Molecular Linker to Better Capture the Endotoxin
  • Abstract Endotoxin is a a very powerful and toxic inflammatory stimulator usually leading to the sepsis occurred. In order to remove endotoxin better through hemoperfusion, it is a pretty choice to increase the length of molecular linker on adsorbents. In this study, we chose the heparin as a molecular linker because of its being anticoagulant linear polysaccharide. Heparin as a linker was covalently immobilized on the chloromethylated polystyrene microspheres (Ps) and then connected with L-phenylalanine (Phe) forming the Ps-Hep-Phe structure to adsorbed endotoxin better. The property of microspheres was characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, zeta potential and… More
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  • Rationally Designed Synthetic Protein Hydrogels with Predictable and Controllable Mechanical Properties
  • Abstract A key challenge in biomaterials research is to produce synthetic hydrogels that can replicate the diverse mechanical properties of the naturally occurring tissues for various biomedical applications, including tissue engineering, stem cell and cancer research, cell therapy, and immunomodulation. However, currently, the methods that can be used to control the mechanical properties of hydrogels are very limited and are mainly focused only on the elasticity of hydrogels. In this work, combining single molecule force spectroscopy, protein engineering and theoretical modeling, we show that synthetic protein hydrogels with predictable mechanical properties can be rationally designed using protein building blocks with known… More
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  • Investigation on Energy Characteristic of RBCs Deformability: A Quantitative Analysis of Extending and Retracting Curves Based on AFM
  • Abstract Deformability is a fundamental property of the cells and tissues of living organisms, which is commonly detected to indicate the state of the cells. And the cell deformability usually depends on the methods that we used, which is easy to be confused. The present research is designed to explore the energy characteristic of red blood cell deformability, based on a quantitative analysis of extending-retracting curves acquired from atomic force microscopy. ATP-depleted red blood cells are prepared by treatment with free-glucose Ringer solution. Our results clearly show that the Youngs’ modulus of erythrocyte is closely depended on the concentration of intracellular… More
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