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.