Cooperativity in septin polymerization is tunable by ionic strength and membrane adsorption

Area of Science:

• Cell biology
• Biophysics
• Polymer science

Background:

• Cells utilize cytoskeletal polymers for essential functions like movement and division.
• Septins, a fourth cytoskeletal component, play roles in membrane dynamics and cell shape but remain poorly understood.
• Understanding septin polymerization is crucial due to their link to various human diseases.

Purpose of the Study:

• To investigate the mechanisms of septin polymer elongation under varying conditions.
• To determine how membranes influence septin polymerization cooperativity.
• To explore the assembly behaviors of septins in solution and on lipid bilayers.

Main Methods:

• Reactive Brownian dynamics simulations to assess membrane-induced cooperativity.
• Fluorescence correlation spectroscopy to evaluate solution-based filament formation at different salt concentrations.
• Quantitative microscopy to study septin membrane adsorption and polymerization on planar and curved lipid bilayers.

Main Results:

• Septins demonstrate salt-dependent cooperative assembly in solution.
• Membrane binding significantly limits septin polymerization cooperativity.
• Septin assembly is highly sensitive to extrinsic conditions and substrate properties.

Conclusions:

• Septin polymerization exhibits characteristics of both isodesmic and cooperative modes.
• The adaptability of septin assembly to different conditions explains their diverse functions and locations.
• Extrinsic factors critically regulate septin assembly, impacting cellular processes.