Abstract
Filopodia are ubiquitous fingerlike protrusions, spawned by many eukaryotic cells, to probe and interact with their environments. Polymerization dynamics of actin filaments, comprising the structural core of filopodia, largely determine their instantaneous lengths and overall lifetimes. The polymerization reactions at the filopodial tip require transport of G-actin, which enter the filopodial tube from the filopodial base and diffuse toward the filament barbed ends near the tip. Actin filaments are mechanically coupled into a tight bundle by cross-linker proteins. Interestingly, many of these proteins are relatively short, restricting the free diffusion of cytosolic G-actin throughout the bundle and, in particular, its penetration into the bundle core. To investigate the effect of steric restrictions on G-actin diffusion by the porous structure of filopodial actin filament bundle, we used a particle-based stochastic simulation approach. We discovered that excluded volume interactions result in partial and then full collapse of central filaments in the bundle, leading to a hollowed-out structure. The latter may further collapse radially due to the activity of cross-linking proteins, hence producing conical-shaped filament bundles. Interestingly, electron microscopy experiments on mature filopodia indeed frequently reveal actin bundles that are narrow at the tip and wider at the base. Overall, our work demonstrates that excluded volume effects in the context of reaction-diffusion processes in porous networks may lead to unexpected geometric growth patterns and complicated, history-dependent dynamics of intermediate metastable configurations.
Highlights
Many eukaryotic cells project dynamic fingerlike protrusions, called filopodia, that are composed of a bundle of actin filaments enveloped by the cellular membrane [1,2]
When filopodial growth dynamics are simulated using the approach described above, we find that, typically, an actin filament bundle undergoes several transitions between metastable configurations
Our results show that the sterically hindered movement of free G-actin molecules leads to intriguing effects: when G-actin cannot pass between filaments in the filopodial shaft bundle, the polymerization of barbed ends of F-actin inside the bundle may not be sufficient to counteract retrograde flow
Summary
Many eukaryotic cells project dynamic fingerlike protrusions, called filopodia, that are composed of a bundle of actin filaments enveloped by the cellular membrane [1,2]. Filopodia play diverse roles across many cell types. Neurons use filopodia in axonal growth cones, to determine the direction of elongation and branching [4], as well as in dendritic spine formation [5]. During wound healing, knitting of filopodia protruding from epithelial cells plays an important role [6]. Filopodia are implicated in cancer progression and metastasis because of their involvement with cell motility [7]. They arise in some viral infections, creating physical connections among the hosts’ cells [8]
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