Colin K. Choi^*, Brian P. Helmke^∗,†

Molecular & Cellular Biomechanics, Vol.5, No.4, pp. 247-258, 2008, DOI:10.3970/mcb.2008.005.247

Abstract Hemodynamic shear stress guides a variety of endothelial phenotype characteristics, including cell morphology, cytoskeletal structure, and gene expression profile. The sensing and processing of extracellular fluid forces may be mediated by mechanotransmission through the actin cytoskeleton network to intracellular locations of signal initiation. In this study, we identify rapid actin-mediated morphological changes in living subconfluent and confluent bovine aortic endothelial cells (ECs) in response to onset of unidirectional steady fluid shear stress (15 dyn/cm²). After flow onset, subconfluent cells exhibited dynamic edge activity in lamellipodia and small ruffles in the downstream and side directions for the… More >

Anat Ratnovsky^∗,†, Matthew Mellema^*, Steven S. An^∗,‡, Jeffrey J. Fredberg^*, Stephanie A. Shore^*

Molecular & Cellular Biomechanics, Vol.4, No.3, pp. 143-158, 2007, DOI:10.3970/mcb.2007.004.143

Abstract Obesity is a risk factor for asthma. The purpose of this study was to determine whether metformin, an agent used in the treatment of an obesity-related condition (type II diabetes), might have therapeutic potential for modifying the effects of obesity on airway smooth muscle (ASM) function. Metformin acts via activation of AMP-activated protein kinase (AMPK), a cellular sensor of energy status. In cultured murine ASM cells, metformin (0.2--2 mM) caused a dose-dependent inhibition of cell proliferation induced by PDGF (10^-8 M) and serotonin (10^-4 M). Another AMPK activator, 5-aminoimidazole-4-carboxamide-1-ß-D-riboruranoside (AICAR), also inhibited PDGF-induced proliferation. Furthermore, cells More >

Judith Su^∗, Xingyu Jiang^†, Roy Welsch^‡, George M. Whitesides^§, Peter T. C. So^¶

Molecular & Cellular Biomechanics, Vol.4, No.2, pp. 87-104, 2007, DOI:10.3970/mcb.2007.004.087

Abstract Interactions between the cell and the extracellular matrix regulate a variety of cellular properties and functions, including cellular rheology. In the present study of cellular adhesion, area was controlled by confining NIH 3T3 fibroblast cells to circular micropatterned islands of defined size. The shear moduli of cells adhering to islands of well defined geometry, as measured by magnetic microrheometry, was found to have a significantly lower variance than those of cells allowed to spread on unpatterned surfaces. We observe that the area of cellular adhesion influences shear modulus. Rheological measurements further indicate that cellular shear… More >

Konstantinos A. Lazopoulos¹, Dimitrije Stamenović²

Molecular & Cellular Biomechanics, Vol.3, No.1, pp. 43-48, 2006, DOI:10.3970/mcb.2006.003.043

Abstract It is well documented that in response to substrate stretching adhering cells alter their orientation. Generally, the cells reorient away from the direction of the maximum substrate strain, depending upon the magnitude of the substrate strain and the state of cell contractility. Theoretical models from the literature can describe only some aspects of this phenomenon. In the present study, we developed a more comprehensive mathematical model of cell reorientation than the current models. Using the framework of theory of non-linear elasticity, we found that the problem of cell reorientation was a stability problem, with the More >

Nan Shen^1,2, Dabajyoti Datta¹, Chris B. Schaffer^1,3,4,5, Eric Mazur^1,6

Molecular & Cellular Biomechanics, Vol.2, No.1, pp. 17-26, 2005, DOI:10.3970/mcb.2005.002.017

Abstract Analysis of cell regulation requires methods for perturbing molecular processes within living cells with spatial discrimination on the nanometer-scale. We present a technique for ablating molecular structures in living cells using low-repetition rate, low-energy femtosecond laser pulses. By tightly focusing these pulses beneath the cell membrane, we ablate cellular material inside the cell through nonlinear processes. We selectively removed sub-micrometer regions of the cytoskeleton and individual mitochondria without altering neighboring structures or compromising cell viability. This nanoscissor technique enables non-invasive manipulation of the structural machinery of living cells with several-hundred-nanometer resolution. Using this approach, we More >

Christopher A. Lemmon^1,2, Nathan J. Sniadecki³, Sami Alom Ruiz^1,3, John L. Tan, Lewis H. Romer^2,4,5, Christopher S. Chen^3,4

Molecular & Cellular Biomechanics, Vol.2, No.1, pp. 1-16, 2005, DOI:10.3970/mcb.2005.002.001

Abstract The interplay of mechanical forces between the extracellular environment and the cytoskeleton drives development, repair, and senescence in many tissues. Quantitative definition of these forces is a vital step in understanding cellular mechanosensing. Microfabricated post array detectors (mPADs) provide direct measurements of cell-generated forces during cell adhesion to extracellular matrix. A new approach to mPAD post labeling, volumetric imaging, and an analysis of post bending mechanics determined that cells apply shear forces and not point moments at the matrix interface. In addition, these forces could be accurately resolved from post deflections by using images of More >

Warren D. Marcus^1,2, Rodger P. McEver³, Cheng Zhu¹

Molecular & Cellular Biomechanics, Vol.1, No.4, pp. 245-252, 2004, DOI:10.3970/mcb.2004.001.245

Abstract When a cell adhered to another cell or substratum via surface proteins is forced to detach, lipid membrane tethers are often extruded from the cell surface before the protein bond dissociates. For example, during the inflammatory reaction leukocytes roll on the surface of activated endothelial cells. The rolling adhesion is mediated by interactions of selectins with their ligands, e.g., P-selectin glycoprotein ligand (PSGL)-1, which extrudes membrane tethers from the surfaces of both leukocytes and endothelial cells. Membrane tether extrusion has been suggested to regulate leukocyte rolling. Here we examine several factors that may affect forces… More >

Tanmay Lele^1,1, Philmo Oh^1,1, Jeffrey A. Nickerson^1,1,2,2, Donald E. Ingber^1,1,3,3

Molecular & Cellular Biomechanics, Vol.1, No.3, pp. 181-190, 2004, DOI:10.3970/mcb.2004.001.181

Abstract The estimation of binding constants and diffusion coefficients of molecules that associate with insoluble molecular scaffolds inside living cells and nuclei has been facilitated by the use of Fluorescence Recovery after Photobleaching (FRAP) in conjunction with mathematical modeling. A critical feature unique to FRAP experiments that has been overlooked by past mathematical treatments is the existence of an `equilibrium constraint': local dynamic equilibrium is not disturbed because photobleaching does not functionally destroy molecules, and hence binding-unbinding proceeds at equilibrium rates. Here we describe an improved mathematical formulation under the equilibrium constraint which provides a more… More >

D.E. Ingber¹

Molecular & Cellular Biomechanics, Vol.1, No.1, pp. 53-68, 2004, DOI:10.3970/mcb.2004.001.053

Abstract This article is a summary of a lecture presented at a symposium on "Mechanics and Chemistry of Biosystems'' in honor of Professor Y.C. Fung that convened at the University of California, Irvine in February 2004. The article reviews work from our laboratory that focuses on the mechanism by which mechanical and chemical signals interplay to control how individual cells decide whether to grow, differentiate, move, or die, and thereby promote pattern formation during tissue morphogenesis. Pursuit of this challenge has required development and application of new microtechnologies, theoretical formulations, computational models and bioinformatics tools. These… More >