Cells Sensing Mechanical Cues: Stiffness Influences the Lifetime of Cell–Extracellular Matrix Interactions by Affecting the Loading Rate

The question of how cells sense substrate mechanical cues has gained increasing attention among biologists. By introducing contour-based data analysis to single-cell force spectroscopy, we identified a loading-rate threshold for the integrin α₂β₁–DGEA bond beyond which a dramatic increase in bond lifetime was observed. On the basis of mechanical cues (elasticity or topography), the effective spring constant of substrates <i>k</i> is mapped to the loading rate <i>r</i> under actomyosin pulling speed <i>v</i>, which, in turn, affects the lifetime of the integrin–ligand bond. Additionally, downregulating <i>v</i> with a low-dose blebbistatin treatment promotes the neuronal lineage specification of mesenchymal stem cells on osteogenic stiff substrates. Thus, sensing of the loading rate is central to how cells sense mechanical cues that affect cell–extracellular matrix interactions and stem cell differentiation