Cruz, I. N.

Cells sense and respond to the mechanical properties of their environment, yet the minimal physical principles sufficient to reproduce mechanotransduction and durotaxis remain debated. This work introduces FraCeMM, a physics-first mechanochemical simulation framework coupling stochastic ligand-integrin-talin binding to a deformable soft-body cell model on an elastic substrate. Without imposed polarity, directional cues, or migration rules, the model reproduces hallmark mechanobiological behaviors including stiffness-dependent spreading, traction reinforcement, focal adhesion asymmetry, and directed durotaxis. A finite pool of adhesion molecules, mechanically coupled through elastic linkages, drives emergent force asymmetry and polarization via self-consistent feedback between stochastic binding, molecular availability, and substrate stiffness. Despite minimal assumptions and a coarse-grained molecular representation, resulting traction forces, adhesion loads, and migration speeds fall within experimentally reported ranges. These results support the view that local force balance, limited adhesion resources, and mechanically binding are sufficient to generate adaptive mechanosensing and directed migration, establishing a transparent and extensible foundation for computational mechanobiology.