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 >

J. P. Mills^1,1, L. Qie^2,2, M. Dao^1,1, C. T. Lim^2,2, S. Suresh^1,3

Molecular & Cellular Biomechanics, Vol.1, No.3, pp. 169-180, 2004, DOI:10.3970/mcb.2004.001.169

Abstract Studies of the deformation characteristics of single biological cells can offer insights into the connections among mechanical state, biochemical response and the onset and progression of diseases. Deformation imposed by optical tweezers provides a useful means for the study of single cell mechanics under a variety of well-controlled stress-states. In this paper, we first critically review recent advances in the study of single cell mechanics employing the optical tweezers method, and assess its significance and limitations in comparison to other experimental tools. We then present new experimental and computational results on shape evolution, force--extension curves, More >

K.Y. Volokh¹

Molecular & Cellular Biomechanics, Vol.1, No.2, pp. 147-160, 2004, DOI:10.3970/mcb.2004.001.147

Abstract A simple phenomenological framework for modeling growth of living tissues is proposed. Growth is defined as a change of mass and configuration of the tissue. Tissue is considered as an open system where mass conservation is violated and the full-scale mass balance is applied. A possible structure of constitutive equations is discussed with reference tosimple growing materials. 'Thermoelastic' formulation of the simple growing material is specified. Within this framework traction free growth of cylindrical and spherical bodies is examined. It is shown that the theory accommodates the case where stresses are not generated in uniform More >

A. Tsourkas, R. Weissleder^1,1

Molecular & Cellular Biomechanics, Vol.1, No.2, pp. 133-146, 2004, DOI:10.3970/mcb.2004.001.133

Abstract Traditionally, fluorescent and luminescent reporter proteins have been used as indicators of gene expression and protein localization. However, insightful mutagenesis and protein engineering strategies have transformed these simple passive reporters into active biological sensors. Molecular reporters are now being designed to alter their intrinsic optical properties in response to specific biomolecular interactions. Applications for these novel biological sensors range from monitoring intracellular pH and ion fluxes to detecting protein-protein interactions and enzymatic activity. The ability to monitor the dynamics of intracellular activity in response to external stimuli can help elucidate the cascade of events involved More >

Kathleen Puskar¹, Leonard Apeltsin², Shlomo Ta’asan³, Russell Schwartz², Philip R. LeDuc⁴

Molecular & Cellular Biomechanics, Vol.1, No.2, pp. 123-132, 2004, DOI:10.3970/mcb.2004.001.123

Abstract Understanding the connection between mechanics and cell structure requires the exploration of the key molecular constituents responsible for cell shape and motility. One of these molecular bridges is the cytoskeleton, which is involved with intracellular organization and mechanotransduction. In order to examine the structure in cells, we have developed a computational technique that is able to probe the self-assembly of actin filaments through a lattice based Monte Carlo method. We have modeled the polymerization of these filaments based upon the interactions of globular actin through a probabilistic model encompassing both inert and active proteins. The More >

M.V. Bayas^1,1, K.Schulten^2,2, D. Leckb,^3,3

Molecular & Cellular Biomechanics, Vol.1, No.2, pp. 101-112, 2004, DOI:10.3970/mcb.2004.001.101

Abstract The force-induced dissociation of the strand dimer interface in C-cadherin has been studied using steered molecular dynamics simulations. The dissociation occurred, without domain unraveling, after the extraction of the conserved trypthophans (Trp2) from their respective hydrophobic pockets. The simulations revealed two stable positions for the Trp2 side chain inside the pocket. The most internal stable position involved a hydrogen bond between the ring Ne of Trp2 and the backbone carbonyl of Glu90. In the second stable position, the aromatic ring is located at the pocket entrance. After extracting the two tryptophans from their pockets, the More >

Leo Q. Wan^1,1, Chester Miller^1,1, X. Edward Guo^2,2, Van C. Mow^1,1,3,3

Molecular & Cellular Biomechanics, Vol.1, No.1, pp. 81-100, 2004, DOI:10.3970/mcb.2004.001.081

Abstract The triphasic constitutive law [Lai, Hou and Mow (1991)] has been shown in some special 1D cases to successfully model the deformational and transport behaviors of charged-hydrated, porous-permeable, soft biological tissues, as typified by articular cartilage. Due to nonlinearities and other mathematical complexities of these equations, few problems for the deformation of such materials have ever been solved analytically. Using a perturbation procedure, we have linearized the triphasic equations with respect to a small imposed axial compressive strain, and obtained an equilibrium solution, as well as a short-time boundary layer solution for the mechano- electrochemical… 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 >

Huajian Gao^1,1, Baohua Ji^1,1, Markus J. Buehler^1,1, Haimin Yao^1,1

Molecular & Cellular Biomechanics, Vol.1, No.1, pp. 37-52, 2004, DOI:10.3970/mcb.2004.001.037

Abstract Bone-like biological materials have achieved superior mechanical properties through hierarchical composite structures of mineral and protein. Gecko and many insects have evolved hierarchical surface structures to achieve extraordinary adhesion capabilities. We show that the nanometer scale plays a key role in allowing these biological systems to achieve their superior properties. We suggest that the principle of flaw tolerance may have had an overarching influence on the evolution of the bulk nanostructure of bone-like materials and the surface nanostructure of gecko-like animal species. We demonstrate that the nanoscale sizes allow the mineral nanoparticles in bone to More >

Gang Bao¹, Andrew Tsourkas², Philip J. Santangelo²

Molecular & Cellular Biomechanics, Vol.1, No.1, pp. 23-36, 2004, DOI:10.3970/mcb.2004.001.023

Abstract The ability to detect, localize, quantify and monitor the expression of specific genes in living cells in real-time will offer unprecedented opportunities for advancement in molecular biology, disease pathophysiology, drug discovery, and medical diagnostics. However, current methods for quantifying gene expression employ either selective amplification (as in PCR) or saturation binding followed by removal of the excess probes (as in microarrays and in situ hybridization) to achieve specificity. Neither approach is applicable when detecting gene transcripts within living cells. Here we review the recent development in engineering nanostructured molecular probes for gene detection in vivo, describe More >