Modelling membrane reshaping by staged polymerization of ESCRT-III filaments

Area of Science:

• Cell Biology
• Biophysics
• Polymer Science

Background:

• The Endosomal Sorting Complexes Required for Transport (ESCRT)-III machinery is crucial for membrane remodeling events, including cell division and viral budding.
• ESCRT-III filaments are known to undergo significant structural and compositional changes, driven by ATP hydrolysis, leading to membrane deformation and scission.
• Understanding the physical principles governing these transformations is key to elucidating their cellular functions.

Purpose of the Study:

• To investigate the physical mechanisms by which ESCRT-III polymer composition changes drive membrane deformation and scission.
• To identify the mechanical conditions required for ESCRT-III mediated membrane neck constriction and vesicle release.
• To model the interplay between polymer dynamics and membrane mechanics during scission.

Main Methods:

• Development of a coarse-grained computational model simulating ESCRT-III polymers and a deformable membrane.
• Modeling ATP-driven stepwise depolymerization of specific ESCRT-III polymers.
• Analysis of membrane morphology transitions (flat, buckled, tubule) and scission efficiency based on polymer composition and depolymerization kinetics.

Main Results:

• Identified specific mechanical regimes where changes in ESCRT-III filament composition trigger membrane shape transitions.
• Demonstrated that ESCRT-III driven membrane deformation progresses from a flat to a buckled state, then to a tubule, culminating in scission.
• Characterized the influence of polymer loss location and timing on membrane deformation extent and scission efficiency.

Conclusions:

• ESCRT-III filaments act as shape-shifting composite polymers capable of severing membrane necks.
• The study reveals near-minimal mechanical conditions necessary for ESCRT-III mediated membrane scission.
• Findings provide insights into the physical basis of membrane neck scission driven by cytoskeletal polymer dynamics.