Steric Effects Induce Geometric Remodeling of Actin Bundles in Filopodia.
Papoian, Garegin A
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Dobramysl, U., Papoian, G. A., & Erban, R. (2016). Steric Effects Induce Geometric Remodeling of Actin Bundles in Filopodia.. Biophysical Journal, 110 (9), 2066-2075. https://doi.org/10.1016/j.bpj.2016.03.013
Filopodia are ubiquitous finger-like 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 towards 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 meta-stable configurations.
Actins, Biomechanical Phenomena, Diffusion, Models, Biological, Protein Multimerization, Protein Structure, Quaternary, Pseudopodia
The research leading to these results has received funding from the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007- 2013) / ERC grant agreement no 239870. R.E. would like to thank the Royal Society for a University Research Fellowship and the Leverhulme Trust for a Philip Leverhulme Prize. This prize money was used to support research visits of G.A.P. in Oxford. His work was also supported by NSF grant CHE-1363081. This work was partially carried out during the visit of R.E. and U.D. to the Isaac Newton Institute. This work was partially supported by a grant from the Simons Foundation. U.D. was also supported by a Junior Interdisciplinary Fellowship via Wellcome Trust grant number 105602/Z/14/Z.
WELLCOME TRUST (105602/Z/14/Z)
External DOI: https://doi.org/10.1016/j.bpj.2016.03.013
This record's URL: https://www.repository.cam.ac.uk/handle/1810/254553
Attribution 2.0 UK: England & Wales, Creative Commons Attribution License 2.0 UK
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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