From Signals to Protrusions: Modeling Excitable Systems in Cell Migration.

Cell migration is a fundamental biological process critical for development, immune response, and wound healing, but its dysregulation contributes to pathological conditions such as cancer metastasis. Recent research has demonstrated that migration is driven by excitable signal transduction and cytoskeletal networks, which function as separate but coupled systems. The signal transduction excitable network (STEN) propagates excitatory signals, while the cytoskeletal excitable network (CEN) generates cytoskeletal protrusions. Although distinct, these networks interact dynamically: STEN regulates CEN, while CEN provides feedback to STEN, influencing cell polarization and directionality. Computational models incorporating nonlinear dynamics and reaction-diffusion systems have successfully recapitulated these interactions, shedding light on their role in pseudopod formation, chemotaxis, and mechanosensation. This review discusses recent experimental and theoretical advances, highlighting how excitable systems underlie cell motility and how mathematical modeling helps to understand their role.