Tunable Integrin–Ligand Coupling Strength Modulates Cellular Adaptive Mechanosensing

Cells sense and respond to the matrix by exerting traction force through binding of integrins to an integrin-specific ligand. Here, Arg−Gly−Asp (RGD) peptide is covalently conjugated to the double-stranded DNA (dsDNA) and stem-loop DNA (slDNA) tethers with a tension tolerance of 43pN and immobilized on a PEG substrate. Unlike dsDNA, which is ruptured under high tension, leading to the removal of RGD, slDNA remains bound even when ruptured. Our results suggest that cells adapt their adhesion state by modulating actin filament polymerization and cofilin phosphorylation, effectively balancing the talin conformation to prevent dsDNA rupture and maintain normal adhesion. This phenomenon, termed integrin–ligand coupling strength, mediated cellular adaptive mechanosensing. Furthermore, we demonstrate that positive durotaxis can shift to negative durotaxis, depending on the integrin–ligand coupling strength. This study highlights the significance of the coupling strength in cell–extracellular matrix (ECM) interactions and offers new insights into designing biomaterials with tunable adhesive properties for cell-based applications.