Modeling insights into subcellular cytoskeleton organization with external size changes

Actin is one of the most abundant proteins in eukaryotic cells and a fundamental component of the cytoskeleton, playing a critical role in maintaining cell structure and enabling motility. A compelling preliminary experimental observation underpins our work: in micropatterned epithelial cells of increasing sizes, the mechanical energy does not scale linearly with size. Instead, an optimal force is generated at a critical cell size, suggesting a force response that combines both passive and active mechanical components. To explore this phenomenon, we present a mechanical model of the actin cytoskeleton in an adherent cell that captures the observed biphasic response in force production, arising from an underlying scaling law in cytoskeletal mechanical properties. Complementing this, we develop an agent-based model that simulates the microscopic dynamics of actin filament formation, incorporating crosslinkers and myosin motors. Within this framework, we test various hypotheses — such as the impact of limited resources — that could give rise to the scaling law identified in the macroscopic model. Together, these efforts constitute a multiscale approach aimed at uncovering the mechanisms by which cell size regulates cytoskeletal force generation.