It is well known that force-induced biological activities play a central role in development and in various disease processes that integrate mechanics and biology. How these mechanical and biochemical pathways interact remains largely unknown. To study the biomechanics of cell function requires a multi-scale and multi-physics approach. Stresses transmitted through adhesion receptors are distributed throughout the cell, leading to conformational changes that occur in individual proteins which in turn lead to increased enzymatic activity or altered binding affinities. The challenge is to couple the macro-scale stresses to micro-scale (individual protein) deformation. We are developing robust computational tools, drawing from molecular dynamics, Brownian dynamics, and large-scale continuum models of mechanics needed to numerically simulate the response of the cytoskeleton to mechanical stimuli. These quantitative models, predicated upon comprehensive and systematic experimental measurements made across multiple length scales, will enable the coupling of continuum with meso- and molecular-level simulations for studying large cellular deformation wherein the whole cell is divided into numerous elements and the response of each element is derived from a concurrent mesoscale simulation consisting of a small number of actin links and actin-binding proteins. (Acknowledgement. This is a collaborative effort with Dr. R.D. Kamm's Laboratory.)