Multi-scale Simulations of Soft Elasticity of the Stem Cell and Its Contact/Focal Adhesion with Extra-cellular Environm

1. Multi-scale Simulations of Soft Elasticity of the Stem Cell and Its Contact/Focal Adhesion with Extra-cellular Environments University of California at Berkeley Shaofan Li The latest discovery in cellular and molecular biology is that the fate or lineage specification of stem cells depend sensitively on both the rigidity as well as surface micro-structures of the extra-cellular environment. For example,Engler et al [2006] reported that matrix elasticity directs stem cell lineage specification. The ability of the cell to sense the environmental mechanical stimulus and subsequently to mediate its own coordinated responses is called Mechanotransduction. The exact molecular mechanism for mechanotransduction to stem cell lineage specification is unknown, and it currently is under active investigation. The objectives of this project are: (1) establishing a Predictive modeling paradigm that can help us understand biomechanics and biophysics the focal adhesion of stem cell, (2) to explain and to elucidate protein conformational changes and binding affinity changes in response to external forces, external ligand perturbations, and mechanical properties of external environment. Even-Ram, S. et al. [2006] Cell and Engler et al. [2006] Cell Microstructures of actin in cells and mesgen in nematic liquid crystals By using a multi-scale approach, we propose a soft elasticity coarse-grained model that combines modeling methods in different scales to study this problem, including molecular dynamics, implicit solvent model,and finite element method of contact mechanics . Liquid crystal elastomer cell model and its finite element Simulation. The basic hypothesis of our approach is: (1) cells including stem cells may be modeled as a special type of liquid crystal elastomer, (2) the cell focal adhesion is induced from contact phase-transformation, and (3) the stem cell lineage specification may be explained by contact induced changes in conformation of protein as well as structural change in cytoskeloton of the stem cell. Different surface elastic stiffness induce different conformation structures as well as global cell structures. External Research Initiative