Mechanical and Kinetic Factors Drive Sorting of Actin Crosslinkers

In cells, actin crosslinkers segregate to different cytoskeletal networks to perform distinct functions, such as forming filopodia to enable cell migration, or polarizing actin bundles to enable cell division. Recent experimental work revealed a passive mechanism that may control this spatial localization: the binding of a short crosslinker to two actin filaments can promote binding of other short crosslinkers and inhibit binding of longer crosslinkers. We hypothesize that this spatial localization is due to the fact that actin is semiflexible and cannot bend over short lengths. We develop a mathematical theory and a Monte Carlo simulation to elucidate the quantitative predictions of this hypothesis. Experiments confirm the predictions but reveal an unanticipated dependence of crosslinker domain size on the kinetics of actin filament polymerization and crosslinker binding affinity. We use simulations of a coarse-grained but molecularly explicit model to characterize the interplay of mechanical and kinetic parameters and understand the observed behavior. Our work demonstrates a physical mechanism by which cells can organize molecular material to drive biological processes, and it can guide the choice and/or design of crosslinkers for protein-based materials.