The More the Tubular: Dynamic Bundling of Actin Filaments for Membrane Tube Formation

Tubular protrusions are a common feature of living cells, arising from polymerization of stiff protein filaments against a comparably soft membrane. Although this process involves many accessory proteins in cells, in vitro experiments indicate that similar tube-like structures can emerge without them, through spontaneous bundling of filaments mediated by the membrane. Using theory and simulation of physical models, we have elaborated how nonequilibrium fluctuations in growth kinetics and membrane shape can yield such protrusions. Enabled by a new grand canonical Monte Carlo method for membrane simulation, our work reveals a cascade of dynamical transitions from individually polymerizing filaments to highly cooperatively growing bundles as a dynamical bottleneck to tube formation. Filament network organization as well as adhesion points to the membrane, which bias filament bending and constrain membrane height fluctuations, screen the effective attractive interactions between filaments, significantly delaying bundling and tube formation.Author Summary: The necessary biophysical conditions for the formation of tubular membrane protrusions by polymerizing actin filament bundles have not yet been fully understood. For this reason we introduce a novel grand canonical simulation model that describes stochastic polymerization of filaments against a fluctuating fluid membrane, while only considering a minimum set of biological proteins. Although still relatively simple and highly tractable, our model explicitly accounts for thermal fluctuations of membrane and filaments, stochastic and quantized polymerization dynamics at the filament tip, cooperativity of multiple filaments, and steric interactions between all model constituents in a physically realistic way. This approach enables us to go well beyond previous static zero-temperature theoretical considerations to filament bundling and explore the physical origins of membrane tube formation dynamics on length and time scales that are currently inaccessible to both experiments and atomistically detailed simulations. Our results suggest a membrane mediated dynamical transition from single filaments to cooperatively growing bundles as an important dynamical bottleneck to tubular protrusion.