Abstract
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.
Highlights
Individual cells generate tubular membrane protrusions in order to sense and interact with their environment [1]
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
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
Summary
Individual cells generate tubular membrane protrusions in order to sense and interact with their environment [1]. In-vitro reconstituted branched actin networks, containing only a minimum set of three purified proteins (i.e. actin, Arp2/3, and N-WASP) and growing from outside against the membrane of a giant unilamellar vesicle, were shown to yield filopodia-like protrusions [4] This finding highlighted the importance of subtle physical interactions between a reduced set of molecular ingredients in bundling filaments and forming membrane tubes. It suggests a much less elaborate mechanism for bundling and protrusion, principally involving effective attractive interactions between neighboring filaments that are mediated by nearby small-amplitude deformations of the membrane due to the individual filaments’ stochastic polymerization (cf Fig 1(a)). When this bundling process eventually accumulates a sufficient number of filaments to overcome membrane resistance, filopodia-like structures emerge
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