Metastable Prepores in Tension-Free Lipid Bilayers

Area of Science:

• Biophysics
• Membrane Science
• Computational Biology

Background:

• Aqueous pore formation and closure in lipid bilayers are fundamental to many biophysical processes.
• Classical nucleation theory adequately describes large pores, but the free-energy landscape of small, biologically relevant pores remains poorly understood.
• The existence of metastable "prepores" has been hypothesized from electroporation experiments, yet theoretical resolution has been challenging.

Purpose of the Study:

• To investigate the conditions under which metastable prepores form in lipid membranes.
• To explore the free-energy landscape of small aqueous pores using computational methods.
• To determine the relationship between lipid molecular structure and prepores metastability.

Main Methods:

• Utilized atomistic simulations to model lipid bilayer behavior.
• Employed self-consistent field theory with a minimal lipid model for theoretical analysis.
• Compared results from both complementary computational approaches.

Main Results:

• Identified the critical role of the relative volume ratio between lipid head groups and tails in pore metastability.
• Found that lipids with larger head-group volume fractions or shorter saturated tails favor metastable prepores.
• Observed that lipids with smaller head-group volume fractions or longer unsaturated tails form unstable prepores.

Conclusions:

• Metastable prepores in lipid membranes are dependent on specific lipid molecular architectures.
• The findings provide a theoretical framework for understanding prepores formation, bridging experimental hypotheses and computational models.
• This research clarifies the parameters governing prepores stability, essential for understanding membrane biophysics.