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The ties that bind us together: the statistical mechanics of cell adhesion proteins
Michael Hinczewski, Case Western Reserve University
For complex multicellular organisms to function, individual cells need mechanisms to bind to each
other. In humans, cell-to-cell adhesion maintains the architecture of tissues, drives the response of the
immune system, and allows for wound healing. All of the contacts involved in these processes are made
through specialized molecules on the surface of cells known as adhesion proteins. These are particularly
interesting from the perspective of statistical physics, since protein bonds are never permanent, but
constantly rupture and reform in a stochastic manner. The distribution of bond lifetimes is intimately
related to the thermal fluctuations in the shape of the protein, and the magnitude of mechanical tension
under which the contact exists. Experiments in the last fifteen years have provided a wealth of data,
including careful measurements of single protein bonds breaking under force. However the data often
introduces as many questions as it answers, revealing strange, counterintuitive phenomena like "catch
bonding", where increasing tension strengthens a bond, prolonging its lifetime. My talk explores the
ways in which nonequilibrium statistical mechanics can help us model and predict adhesion protein
dynamics, exploiting simple, analytically solvable theories of diffusion on multidimensional energy
landscapes. The theory gives us a surprisingly detailed perspective on the molecular interactions that
underlie bonding, and highlights the critical role of randomness in biological functions.