article published yes Xiuyun Jiang author Lena Harker-Kirschneck author Christian Eduardo Vanhille-Campos author 3adeca52-9313-11ed-b1ac-c170b2505714 Anna-Katharina Pfitzner author Elene Lominadze author Aurélien Roux author Buzz Baum author Anđela Šarić author bf63d406-f056-11eb-b41d-f263a6566d8b0000-0002-7854-2139 AnSa department Non-Equilibrium Protein Assembly: from Building Blocks to Biological Machines project The evolution of trafficking: from archaea to eukaryotes project 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. https://research-explorer.ista.ac.at/download/12152/12359/2022_PLoSCompBio_Jiang.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Public Library of Science2022 eng Computational Theory and MathematicsCellular and Molecular NeuroscienceGeneticsMolecular BiologyEcologyModeling and SimulationEcologyEvolutionBehavior and Systematics 1553-7358 36251703 00092488550000510.1371/journal.pcbi.1010586 1810 https://github.com/sharonJXY/3-filament-model X. Jiang, L. Harker-Kirschneck, C.E. Vanhille-Campos, A.-K. Pfitzner, E. Lominadze, A. Roux, B. Baum, A. Šarić, PLOS Computational Biology 18 (2022). Jiang X, Harker-Kirschneck L, Vanhille-Campos CE, Pfitzner A-K, Lominadze E, Roux A, Baum B, Šarić A. 2022. Modelling membrane reshaping by staged polymerization of ESCRT-III filaments. PLOS Computational Biology. 18(10), e1010586. Jiang, Xiuyun, et al. “Modelling Membrane Reshaping by Staged Polymerization of ESCRT-III Filaments.” <i>PLOS Computational Biology</i>, vol. 18, no. 10, e1010586, Public Library of Science, 2022, doi:<a href="https://doi.org/10.1371/journal.pcbi.1010586">10.1371/journal.pcbi.1010586</a>. X. Jiang <i>et al.</i>, “Modelling membrane reshaping by staged polymerization of ESCRT-III filaments,” <i>PLOS Computational Biology</i>, vol. 18, no. 10. Public Library of Science, 2022. Jiang X, Harker-Kirschneck L, Vanhille-Campos CE, et al. Modelling membrane reshaping by staged polymerization of ESCRT-III filaments. <i>PLOS Computational Biology</i>. 2022;18(10). doi:<a href="https://doi.org/10.1371/journal.pcbi.1010586">10.1371/journal.pcbi.1010586</a> Jiang, Xiuyun, Lena Harker-Kirschneck, Christian Eduardo Vanhille-Campos, Anna-Katharina Pfitzner, Elene Lominadze, Aurélien Roux, Buzz Baum, and Anđela Šarić. “Modelling Membrane Reshaping by Staged Polymerization of ESCRT-III Filaments.” <i>PLOS Computational Biology</i>. Public Library of Science, 2022. <a href="https://doi.org/10.1371/journal.pcbi.1010586">https://doi.org/10.1371/journal.pcbi.1010586</a>. Jiang, X., Harker-Kirschneck, L., Vanhille-Campos, C. E., Pfitzner, A.-K., Lominadze, E., Roux, A., … Šarić, A. (2022). Modelling membrane reshaping by staged polymerization of ESCRT-III filaments. <i>PLOS Computational Biology</i>. Public Library of Science. <a href="https://doi.org/10.1371/journal.pcbi.1010586">https://doi.org/10.1371/journal.pcbi.1010586</a> 121522023-01-12T12:08:10Z2025-06-12T06:19:28Z