PT  - JOURNAL ARTICLE
AU  - Lena Harker-Kirschneck
AU  - Buzz Baum
AU  - Andela Šarić
TI  - Changes in ESCRT-III filament geometry drive membrane remodelling and fission <em>in sillico</em>
AID  - 10.1101/559898
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 559898
4099  - http://biorxiv.org/content/early/2019/09/10/559898.short
4100  - http://biorxiv.org/content/early/2019/09/10/559898.full
AB  - ESCRT-III is a membrane remodelling filament with the unique ability to cut membranes from the inside of the membrane neck. It is essential for the final stage of cell division, the formation of vesicles, the release of viruses, and membrane repair. Distinct to other cytoskeletal filaments, ESCRT-III filaments do not consume energy, but work in conjunction with another ATP-consuming complex. Despite rapid progress in describing the cell biology of ESCRT-III, we lack an understanding of the physical mechanisms behind its force production and membrane remodelling. Here we present a minimal coarse-grained model that that captures all the experimentally reported cases of ESCRT-III driven membrane sculpting, including the formation of downward and up-ward cones and tubules. This model suggests that a change in the geometry of membrane bound ESCRT-III filaments induces transitions between a flat spiral and a 3D helix to drive membrane deformation. We then show that such repetitive filament geometry transitions can induce the fission of cargo-containing vesicles. The mechanistic principles revealed here will enable manipulation of ESCRT-III-driven processes in cells and in guiding the engineering of synthetic membrane-sculpting systems.