Biology subjects

Vanhille Campos, C.

Publications and source records attributed to Vanhille Campos, C..

5 recordsLinked to original sources

bioRxiv2026

Design and self-assembly of cytomotive filaments

Cytomotive filaments such as actin and FtsZ exhibit treadmilling, a turnover mode in which subunits are added at one end and removed from the other, driven by nucleotide hydrolysis. This dynamics, which requires directional filament growth and disassembly without fragmentation, is crucial for the function of these filaments. However, how treadmilling is encoded in the monomer properties remains unclear. Here we combine physical modelling with in silico evolution to identify the minimal monomer design principles that yield treadmilling. We show that directional growth requires a polymerization-induced change in the binding interface of the monomer. Fragmentation-free disassembly further requires that this conformational change allosterically couples two monomer interfaces that bind it to its left and right neighbours. Guided by these principles, we design a minimal particle-based monomer that spontaneously assembles into treadmilling filaments in simulations. This work establishes a physical framework for cytomotive filament dynamics and provides a foundation for engineering synthetic systems with controllable emerging treadmilling dynamics. Significance statementTreadmilling, the continuous, energy-driven assembly and disassembly of monomers at opposite ends of a filament, is a fundamental dynamic of the cytoskeleton across the tree of life. How can individual monomers self-assemble into a polar filament that grows at one end and shrinks at the other? By combining physical modelling and in silico evolution, we uncover the physical and geometrical principles that monomers must satisfy to naturally form treadmilling filaments. In particular, we show that polar assembly requires monomers to undergo a conformational change upon assembly. In turn, controlled filament disassembly requires this conformational change to geometrically couple a monomers two binding interfaces, preventing filament fragmentation. Our work provides a physical framework for designing functional self-assembling materials.

biophysics↗

bioRxiv2023

Self-organisation of mortal filaments: the role of FtsZ treadmilling in bacterial division ring formation

Protein filaments in the cell commonly treadmill - they grow on one end while shrinking on the other, driven by energy consumption. Treadmilling filaments appear to be moving, even though individual proteins remain static. Here, we investigate the role of treadmilling, implemented as dynamic turnover, in the collective filament self-organisation. On the example of the bacterial FtsZ protein, a highly conserved tubulin homologue, we show, in computer simulations and in vitro experiments, that treadmilling drives filament nematic ordering by dissolving misaligned filaments. We demonstrate that ordering via local dissolution allows the system to quickly respond to chemical and geometrical biases in the cell, and is necessary for the formation of the FtsZ ring required for bacterial cell division in living Bacillus subtilis cells. We finally use simulations to quantitatively explain the characteristic dynamics of FtsZ ring formation in vivo. Beyond FtsZ and other cytoskeletal filaments, our study identifies a novel mechanism for nematic ordering via constant birth and death of energy-consuming filaments.

biophysics↗

bioRxiv2022

Modelling Membrane Reshaping by Staged Polymerization of ESCRT-III Filaments

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. Author summaryESCRT-III proteins have the unique ability to cut membrane necks from within, which is needed for a vast number of cell remodelling events including the release of cargo-containing vesicles. ESCRT-III proteins exist in different forms, which can assemble into spiral and helical homopolymers of different curvatures, and they have been suggested to polymerize and depolymerize with each other in a staged manner to deform and cut membranes. We developed a computer model to explore the physical mechanisms behind vesicle budding driven by the staged assembly and disassembly of multiple elastic filaments. We identified rules that determine the outcomes of membrane remodelling, which depend on the relative physical features of the distinct filaments, the dynamics of their disassembly, and on the presence of cargo; thereby providing experimentally testable predictions. Our study provides new physical insights into the ESCRT-III-mediated vesicle budding process, at a single subunit level, and identifies the general design principles of nanomachines built from shapeshifting copolymers, which might also be realized in synthetic systems.

biophysics↗

bioRxiv2021

Physical mechanisms of ESCRT-III-driven cell division in archaea

Living systems propagate by undergoing rounds of cell growth and division. Cell division is at heart a physical process that requires mechanical forces, usually exerted by protein assemblies. Here we developed the first physical model for the division of archaeal cells, which despite their structural simplicity share machinery and evolutionary origins with eukaryotes. We show how active geometry changes of elastic ESCRT-III filaments, coupled to filament disassembly, are sufficient to efficiently split the cell. We explore how the non-equilibrium processes that govern the filament behaviour impact the resulting cell division. We show how a quantitative comparison between our simulations and dynamic data for ESCRTIII-mediated division in Sulfolobus acidocaldarius, the closest archaeal relative to eukaryotic cells that can currently be cultured in the lab, and reveal the most likely physical mechanism behind its division.

biophysics↗

bioRxiv2020

Dynamics of vesicle reshaping and scission under osmotic shocks

We study the effects of osmotic shocks on lipid vesicles via coarse-grained molecular dynamics simulations by explicitly considering the solute in the system. We find that depending on their nature (hypo- or hypertonic) such shocks can lead to bursting events or engulfing of external material into inner compartments, among other morphology transformations. We characterize the dynamics of these processes and observe a separation of time scales between the osmotic shock absorption and the shape relaxation. Our work consequently provides an insight into the dynamics of compartmentalization in vesicular systems as a result of osmotic shocks, which can be of interest in the context of early proto-cell development and proto-cell compartmentalisation.

biophysics↗