Tension-induced vesicle fusion: pathways and pore dynamics

Area of Science:

• Biophysics
• Computational Biology
• Membrane Dynamics

Background:

• Vesicle fusion is a fundamental biological process.
• Understanding the role of membrane tension in fusion dynamics is crucial.
• Previous simulation studies have primarily focused on stalk-mediated fusion pathways.

Purpose of the Study:

• To investigate the dynamics of tension-induced fusion of two vesicles using advanced simulation techniques.
• To identify and characterize distinct fusion pathways under varying membrane tension conditions.
• To quantify the energy barriers and fusion pore dynamics involved in vesicle fusion.

Main Methods:

• Utilized dissipative particle dynamics (DPD) simulations with an improved parameter set for vesicle membranes.
• Simulated vesicle fusion over microsecond timescales, allowing for membrane area stretch up to 10-30% before rupture.
• Analyzed fusion pathways, pore formation, and statistical dependence of fusion time on membrane tension.

Main Results:

• Observed two distinct fusion pathways: Pathway I (low tension, no stalk formation) and Pathway II (higher tension, stalk formation).
• Pathway I involves a flattened adhesion zone and hemifusion intermediate, distinct from previously described stalk pathways.
• Fusion was identified as the dominant mechanism for vesicle tension release, with fusion time dependent on overcoming energy barriers of 13kBT and 11kBT.

Conclusions:

• Membrane tension significantly influences vesicle fusion pathways, with a novel non-stalk pathway identified at lower tensions.
• The study provides quantitative insights into fusion dynamics, including energy barriers and fusion pore radius evolution, aligning with experimental data.
• These findings enhance the understanding of membrane fusion mechanisms and their regulation by mechanical forces.