Ligand Mobility-Mediated Cell Adhesion and Spreading

Cells live in a highly dynamic environment where their physical connection and communication with the outside are achieved through receptor-ligands binding. Therefore, a precise knowledge of the interaction between receptors and ligands is critical for our understanding of how cells execute different biological duties. Interestingly, recent evidence has shown that the mobility of ligands at the cell-extracellular matrix (ECM) interface significantly affects the adhesion and spreading of cells, while the underlying mechanism remains unclear. Here, we present a modeling investigation to address this critical issue. Specifically, by adopting the Langevin dynamics, the random movement of ligands was captured by assigning a stochastic force along with a viscous drag on them. After that, the evolution of adhesion and subsequent spreading of cells were analyzed by considering the force-regulated binding/breakage of individual molecular bonds connecting polymerizing actin bundles inside the cell to the ECM. Interestingly, a biphasic relationship between adhesion and ligand diffusivity was predicted, resulting in maximized cell spreading at intermediate mobility of ligand molecules. In addition, this peak position was found to be dictated by the aggregation of ligands, effectively reducing their diffusivity, and how fast bond association/dissociation can occur. These predictions are in excellent agreement with our experimental observations where distinct ligand mobility was introduced by tuning the interactions between the self-assembly polymer coating and the surface.

Automated summary

Cells rely on receptor-ligand binding to connect and communicate with the external environment. Understanding the interaction between receptors and ligands is crucial for comprehending cellular biology. Recent evidence suggests that the mobility of ligands at the cell-ECM interface affects cell adhesion and spreading, but the underlying mechanism is unclear. This modeling investigation reveals a biphasic relationship between adhesion and ligand diffusivity, with peak spreading observed at intermediate ligand mobility. The aggregation of ligands and the kinetics of bond association/dissociation play a role in determining this peak position.