Exploring the Energetics of Membrane Fission Using Molecular Simulations

Area of Science:

• Biophysics
• Cell Biology
• Computational Biology

Background:

• Membrane fission is crucial for cellular processes like trafficking and division.
• The energy landscape of fission intermediates (hemifission, rupture) is not well understood.
• Understanding fission energetics is key to cellular function and dysfunction.

Purpose of the Study:

• To map the free-energy landscape of membrane fission in lipid bilayers.
• To investigate the influence of physical and chemical factors on fission energetics.
• To provide a mechanistic framework for membrane fission.

Main Methods:

• Coarse-grained molecular dynamics simulations.
• Free-energy calculations using a collective variable (reaction coordinate).
• Analysis of intact-to-hemifission and hemifission-to-rupture transitions.

Main Results:

• Tube radius impacts fission barriers: hemifission barrier increases, rupture barrier decreases.
• Lipid composition (DOPE vs. DOPC) affects hemifission stability.
• Membrane tension significantly lowers the hemifission barrier.
• Influenza A M2 protein was shown to lower the hemifission energy barrier.

Conclusions:

• Provides a simulation framework to study membrane fission energetics.
• Demonstrates how lipid properties, protein interactions, and tension modulate fission.
• Offers mechanistic insights into viral budding and cellular trafficking.