title: Elastohydrodynamics and Kinetics of Protein Patterning in the Immunological Synapse.
abstract: We propose a minimal mathematical model for the physical basis of membrane protein patterning in the immunological synapse (IS), which encompass membrane mechanics, protein binding kinetics and motion, and fluid flow in the synaptic cleft. Our theory leads to simple predictions for the spatial and temporal scales of protein cluster formation, growth and arrest as a function of membrane stiffness, rigidity and kinetics of the adhesive proteins, and the fluid flow in the synaptic cleft. Numerical simulations complement these scaling laws by quantifying the nucleation, growth and stabilization of proteins domains on the size of the cell. Direct comparison with experiment shows that passive elastohydrodynamics and kinetics of protein binding in the synaptic cleft can describe the short-time formation and organization of protein clusters, without evoking any active processes in the cytoskeleton. Despite the apparent complexity of the process, our analysis shows that just two dimensionless parameters characterize the spatial and temporal evolution of the protein pattern: a ratio of membrane elasticity to protein stiffness, and the ratio of a hydrodynamic time scale for fluid flow relative to the protein binding rate. A simple phase diagram encompasses the variety of patterns that can arise.
authors.affiliation: School of Engineering and Applied Sciences, Kavli Institute for Bionano Science and Technology, and Wyss Institute, Harvard University, Cambridge, United States of America.
authors.forename: Andreas
authors.initials: A
authors.lastname: Carlson
authors.affiliation: School of Engineering and Applied Sciences, Kavli Institute for Bionano Science and Technology, and Wyss Institute, Harvard University, Cambridge, United States of America.|Departments of Physics, and Organismic and Evolutionary Biology, Harvard University, Cambridge, United States of America.
authors.forename: L
authors.initials: L
authors.lastname: Mahadevan
mesh_terms: D000938:Antigen-Presenting Cells / Q000737:chemistry* / Q000276:immunology; D003198:Computer Simulation; D055119:Elastic Modulus; D006801:Humans; D057446:Hydrodynamics; D054992:Immunological Synapses; D008051:Lipid Bilayers / Q000737:chemistry* / Q000276:immunology; D040542:Mechanotransduction, Cellular / Q000276:immunology; D008560:Membrane Fluidity / Q000276:immunology; D008565:Membrane Proteins / Q000737:chemistry* / Q000276:immunology; D008956:Models, Chemical; D018448:Models, Immunological; D008958:Models, Molecular; D011485:Protein Binding; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D013718:Tensile Strength
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins