title: Steric Effects Induce Geometric Remodeling of Actin Bundles in Filopodia.
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.
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dobramysl
authors.affiliation: Department of Chemistry & Biochemistry, University of Maryland, College Park, Maryland. Electronic address: gpapoian@umd.edu.
authors.forename: Garegin A
authors.initials: GA
authors.lastname: Papoian
authors.affiliation: Mathematical Institute, University of Oxford, Radcliffe Observatory Quarter, Oxford, United Kingdom. Electronic address: erban@maths.ox.ac.uk.
authors.forename: Radek
authors.initials: R
authors.lastname: Erban
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D001696:Biomechanical Phenomena; D004058:Diffusion; D008954:Models, Biological; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011554:Pseudopodia / Q000378:metabolism*
chemical_list: D000199:Actins