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 the fastest, while the statistically dominant transition path undergoes a qualitative change—the entropic barrier to a completely bound or unbound state 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 quasistatic and kinetic responses to changes in the membrane stiffness or applied forces is largest near the statical and dynamical critical points, respectively.
- Received 5 November 2020
- Revised 17 June 2021
- Accepted 29 July 2021
DOI:https://doi.org/10.1103/PhysRevX.11.031067
Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI. Open access publication funded by the Max Planck Society.
Published by the American Physical Society
Physics Subject Headings (PhySH)
Popular Summary
Cell adhesion—the binding of cells to neighboring cells or the extracellular matrix—is essential for many biological processes. Central to cell adhesion is cellular mechanics, in particular, the rigidity of cell membranes. Researchers have a good understanding of why fluctuations of cell membranes introduce correlations in the dynamics of adhesion bonds. However, what remains elusive is how cooperativity affects structure, stability, dynamics of adhesion domains, and their response to mechanical forces arising during physiological or pathological processes. Our work explains the collective effects underpinning cell adhesion under the action of external forces, and it argues that these are relevant for tissue remodeling, cancer metastasis, and the immune response.
We consider a 2D lattice model of anchored as well as mobile interacting adhesion bonds with an intrinsic binding affinity under the action of a shared force. We obtain analytical results for the thermodynamics and kinetics of adhesion clusters of any size, ranging from very few adhesion bonds to a sufficiently large number of bonds where any surface or edge effects are negligible. We prove the existence of a novel dynamical phase transition at which cluster formation and dissolution are fastest, and the collective dynamics undergoes a qualitative change. The response to changes in membrane rigidity or applied forces is largest at criticality, which may have biological implications such as for the metastatic potential of cancer cells or the ability of immune cells to recognize and adhere to pathogens.
Our results are not only relevant to biological physics and cellular and molecular biology but are also general enough to impact nonequilibrium statistical physics.
