Effects of Ligand Mobility on Ligand-Receptor Interactions Driving Integrin-Mediated Cell Adhesion.

Ligand-receptor interactions that drive cell adhesion occur within dynamic membrane environments, where ligand mobility can influence force transmission and downstream signaling. Despite its potential significance, the mechanical role of ligand mobility in regulating the activation threshold for cell adhesion remains poorly understood. Here, we quantified how ligand mobility modulates the apparent adhesion threshold for integrin-mediated cell adhesion using DNA-based tension gauge tethers. By directly comparing mobile ligands presented on supported lipid bilayers with immobilized ligands on rigid substrates, we demonstrated that mobile ligands exhibited apparent adhesion thresholds consistently lower than those of immobile ligands across multiple cell types. Controlled modulation of membrane fluidity further revealed that the ligand diffusion constants are inversely proportional to apparent adhesion thresholds. These results highlight the critical role of ligand mobility in ligand-receptor interactions and advance our understanding of how membrane physical properties regulate cellular signaling.