Title: Criticality in Cell Adhesion

Abstract: We illuminate the many-body effects underlying the structure, formation, and dissolution of cellular adhesion domains in the presence and absence of forces. We consider mixed Glauber-Kawasaki dynamics of a two-dimensional model of nearest-neighbor interacting adhesion bonds with intrinsic binding-affinity under the action of a shared pulling or pushing force. We consider adhesion bonds that are immobile due to being anchored to the underlying cytoskeleton as well as adhesion molecules that are transiently diffusing. Highly accurate analytical results are obtained on the pair-correlation level of the Bethe-Guggenheim approximation for the complete thermodynamics and kinetics of adhesion clusters of any size, including the thermodynamic limit. A new kind of dynamical phase transition is uncovered -- the mean formation and dissolution times per adhesion bond change discontinuously with respect to the bond-coupling parameter. At the respective critical points cluster formation and dissolution are fastest, while the statistically dominant transition path undergoes a qualitative change -- the entropic barrier to complete binding/unbinding is rate-limiting below, and the phase transition between dense and dilute phases above the dynamical critical point. In the context of the Ising model the dynamical phase transition reflects a first-order discontinuity in the magnetization-reversal time. Our results provide a potential explanation for the mechanical regulation of cell adhesion, and suggest that the quasi-static and kinetic response to changes in the membrane stiffness or applied forces is largest near the statical and dynamical critical point, respectively.