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Chemomechanical characteristics of the extracellular materials with which cells interact can have a profound impact on cell adhesion and migration. To understand and modulate such complex multiscale processes, a detailed understanding of the feedback between a cell and the adjacent microenvironment is crucial. Here, we use computational modeling and simulation to examine the cell-matrix interaction at both the molecular and continuum lengthscales. Using steered molecular dynamics, we consider how extracellular matrix (ECM) stiffness and extracellular pH influence the interaction between cell surface adhesion receptors and extracellular matrix ligands, and we predict potential consequences for focal adhesion formation and dissolution. Using continuum level finite element simulations and analytical methods to model cell-induced ECM deformation as a function of ECM stiffness and thickness, we consider the implications toward design of synthetic substrata for cell biology experiments that intend to decouple chemical and mechanical cues.

The function of tissue cells can be significantly modulated by changes in the local mechanical environment, including the stiffness of the substrata to which these cells adhere. To engineer surfaces that maintain or induce cell functions, it is important to understand the force, length, and timescales over which cell surface receptors probe the local mechanical environment. Here we show how simplified continuum and atomistic simulations of the nanoscale forces between cell surface receptors and extracellular matrix molecules help define the critical features of materials designed to recapitulate the cell's in vivo mechanical environment for tissue engineering applications.