Regulation of Cell Adhesion Free Energy by External Sliding Forces

Cells experience a variety of forces and external velocities in vivo. While a number of continuum based models have addressed cell substrate interactions in these dynamic environments, a molecular picture of adhesion under external sliding forces and velocities is lacking. Using a molecular thermodynamic model, that incorporates entropic and steric repulsions, molecular conformations and constraints, penetrable substrates and explicit binding interactions, we study the effect of external sliding velocities on cell adhesion. We map the free energy landscapes under a broad range of external forces, binding energies and receptor surface coverages. Our calculations predict the regimes where free energy landscapes become resistant to external forces. Our model shows good agreement with experimental studies and lays out a scalable framework for analyzing and quantifying a broad spectrum of in vivo and in vitro adhesion studies.