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Modelling membrane reshaping by staged polymerization of ESCRT-III filaments

Jiang, Xiuyun; Harker-Kirschneck, Lena; Vanhille-Campos, Christian; Pfitzner, Anna-Katharina; Lominadze, Elene; Roux, Aurélien; Baum, Buzz; (2022) Modelling membrane reshaping by staged polymerization of ESCRT-III filaments. PLOS Computational Biology , 18 (10) , Article e1010586. 10.1371/journal.pcbi.1010586. Green open access

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Abstract

ESCRT-III filaments are composite cytoskeletal polymers that can constrict and cut cell membranes from the inside of the membrane neck. Membrane-bound ESCRT-III filaments undergo a series of dramatic composition and geometry changes in the presence of an ATP-consuming Vps4 enzyme, which causes stepwise changes in the membrane morphology. We set out to understand the physical mechanisms involved in translating the changes in ESCRT-III polymer composition into membrane deformation. We have built a coarse-grained model in which ESCRT-III polymers of different geometries and mechanical properties are allowed to copolymerise and bind to a deformable membrane. By modelling ATP-driven stepwise depolymerisation of specific polymers, we identify mechanical regimes in which changes in filament composition trigger the associated membrane transition from a flat to a buckled state, and then to a tubule state that eventually undergoes scission to release a small cargo-loaded vesicle. We then characterise how the location and kinetics of polymer loss affects the extent of membrane deformation and the efficiency of membrane neck scission. Our results identify the near-minimal mechanical conditions for the operation of shape-shifting composite polymers that sever membrane necks.

Type: Article
Title: Modelling membrane reshaping by staged polymerization of ESCRT-III filaments
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pcbi.1010586
Publisher version: https://doi.org/10.1371/journal.pcbi.1010586
Language: English
Additional information: © 2022 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10158439
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