Polymer-like model to study the dynamics of dynamin filaments on deformable membrane tubes

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Item Type:	Article
Title:	Polymer-like model to study the dynamics of dynamin filaments on deformable membrane tubes
Creators Name:	Noel, J.K., Noé, F., Daumke, O. and Mikhailov, A.S.
Abstract:	Peripheral membrane proteins with intrinsic curvature can act both as sensors of membrane curvature and shape modulators of the underlying membranes. A well-studied example of such proteins is the mechanochemical GTPase dynamin, which assembles into helical filaments around membrane tubes and catalyzes their scission in a GTPase-dependent manner. It is known that the dynamin coat alone, without GTP, can constrict membrane tubes to radii of ~10 nm, indicating that the intrinsic shape and elasticity of dynamin filaments should play an important role in membrane remodeling. However, molecular and dynamic understanding of the process is lacking. Here, we develop a dynamical polymer-chain model for a helical elastic filament bound on a deformable membrane tube of conserved mass, accounting for thermal fluctuations in the filament and lipid flows in the membrane. The model is based on the locally cylindrical helix approximation for dynamin. We obtain the elastic parameters of the dynamin filament by molecular dynamics simulations of its tetrameric building block and also from coarse-grained structure-based simulations of a 17-dimer filament. The results show that the stiffness of dynamin is comparable to that of the membrane. We determine equilibrium shapes of the filament and the membrane and find that mostly the pitch of the filament, not its radius, is sensitive to variations in membrane tension and stiffness. The close correspondence between experimental estimates of the inner tube radius and those predicted by the model suggests that dynamin's "stalk" region is responsible for its GTP-independent membrane-shaping ability. The model paves the way for future mesoscopic modeling of dynamin with explicit motor function.
Keywords:	Biological Models, Biomechanical Phenomena, Cell Membrane, Dynamins, Elasticity, Molecular Dynamics Simulation, Polymers, Temperature, Time Factors
Source:	Biophysical Journal
ISSN:	0006-3495
Publisher:	Cell Press
Volume:	117
Number:	10
Page Range:	1870-1891
Date:	19 November 2019
Additional Information:	This article will also be published in open access. It has a delayed release (embargo) and will be available in PMC on November 19 1, 2020.
Official Publication:	https://doi.org/10.1016/j.bpj.2019.09.042
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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