Mathematical Biology seminar Tamara Bidone University of Utah "Modeling Emergent Cellular Responses: The Critical Role of Kinetics in Mechanically Active Adhesion Proteins" Tuesday, January 13, 2026 1-2pm in LCB 215 Abstract: Biological systems rely on mechanical elements that are not only passive but also actively regulated, and emergent cellular behaviors often arise from the interplay between mechanics and kinetics. Integrins, adhesion receptors that switch between inactive and active conformations, exemplify this principle: ligand binding and mechanosensitive cell spreading depend not only on their stiffness but also on activation dynamics. We investigated how integrin mechanical properties and activation kinetics shape cell spreading using a multiscale approach. Brownian dynamics simulations revealed that while substrate rigidity enhances spreading, the extent of spreading on soft substrates is insensitive to integrin stiffness alone. All-atom molecular dynamics and potential of mean force calculations showed that an activating β3 S243E mutation broadens the conformational landscape, increasing the propensity for force-induced extension. Translating this into effective activation rates demonstrated that kinetics, rather than passive mechanics, govern spreading on soft substrates. These findings highlight that capturing emergent mechanosensitive behaviors in biological systems requires modeling both passive mechanical elements and their dynamic, kinetic regulation, emphasizing the critical role of activation dynamics in determining cellular responses.