Effects of adhesion pattern of 2D substrate on cell morphology and migration

Focal adhesions play critical roles in a variety of cellular behaviors and physiological processes, including cell migration, proliferation, wound healing, and tumor invasion. Although focal adhesions are recognized as key protein signaling and mechanosensory hubs that mediate interactions between the cell and the extracellular matrix (ECM), the mechanisms by which cells sense and respond to ECM geometry at the subcellular level, and how these cues are translated into cell-scale behaviors, remain unclear. In this study, we develop a computational cell model to investigate the effects of adhesion pattern of 2D substrate on cell morphology and migration. The model has several advancements over existing approaches, including the incorporation of cellular viscoelasticity, dynamic cell-substrate communication, and a mechano-chemical feedback loop between cell adhesion and protrusion. The simulation results are directly compared with the experimental data and show remarkable agreement. Based on both simulations and validated experiments involving cells on substrate with directional patterns under Y-27632 and sh-β Pix treatments, we propose that line tension along the cell boundary, driven by contractility, plays a dominant role in driving directed cell migration. Additionally, focal-adhesion-mediated protrusion through chemical signaling supplements to maintain the migration directionality. These findings provide useful insights into the underlying mechanism of the effects of cell-ECM-regulated mechano-chemical interactions on cell morphology and migration.