Mechanochemical Rules for Shape-Shifting Filaments that Remodel Membranes

Roles of ESCRT-III polymers in cell division across the tree of life

“…Importantly, since sequential changes in filament composition translate into changes in polymer structure, the diameter of composite filaments can narrow over time to constrict the membrane tube to which it is bound. The idea that sequential changes in ESCRT-III copolymer structure might drive membrane remodelling in this way aligns well with theory and coarse-grained molecular dynamics simulations [ 19 , 69 , 72 , 73 ]. Such models show how shifts in filament geometry and in the orientation of the polymer’s membrane binding surfaces can drive the transition from flat spirals to helices that disassemble to induce fission.…”

“…This is possible because from archaea to eukaryota, all cells co-express multiple different ESCRT-III isoforms. The coming and going of individual ESCRT-III proteins drives sequential changes in the structure of the composite polymer [ 67 – 69 ], which are thought to guide the membrane through a series of different states from deformation, to construction and fission. Importantly, a similar type of behaviour has been observed in reconstituted systems.…”

“…In an extension of these analyses, Roux et al found that when different ESCRT-III monomers were pre-mixed with the ESCRT-associated AAA–ATPase, Vps4, and added to membranes in vitro , the polymers formed underwent changes in composition as different ESCRT-III monomers were incorporated and removed in sequence [ 67 ]. Because the changes in subunit incorporation occurred in a fixed order, this has the potential to ensure that membrane remodelling proceeds to completion [ 67 , 69 ]. Several factors likely contribute to the precise ordering of ESCRT-III monomer recruitment and release in this case.…”

“…During the process of eukaryogenesis, homologues of ESCRT-IIIA and ESCRT-IIIB appear to have given rise to the two major families of eukaryotic ESCRT-III proteins, named CHMP1-3 and CHMP4-7 families respectively [ 99 , 101 , 102 ]. The later divergence of these ESCRT-III family proteins in eukaryotes ( Figure 1 ) likely widened the range of spatial scales over which they can act, reduced the energetic barrier to membrane remodelling [ 69 ] and enabled specific ESCRT-III isoforms to adapt to specific eukaryotic contexts, e.g. nuclear envelope sealing [ 103 ].…”

Theoretical and Data-Driven Approaches for Biomolecular Condensates

“…139 Building hypothesized constraints into a model makes it possible to test whether those constraints are sufficient to reproduce key experimental observations. These types of ground-up models are helpful for identifying the driving forces of a variety of processes, and have been used to study a range of processes from protein-driven membrane deformation and cell division 140,141 to collagen self-assembly 142 and the phase separation in many-component systems with a range of intermolecular interactions. 45 While useful for focused investigations, these models are system-specific by nature, so they cannot be as readily applied to other types of systems.…”