Intrinsic Lipid Curvature and Bilayer Elasticity as Regulators of Channel Function: A Comparative Single-Molecule...

Area of Science:

• Biophysics
• Membrane Biophysics
• Protein-Lipid Interactions

Background:

• Bilayer material properties, including thickness, lipid intrinsic curvature, and elastic moduli, influence membrane protein conformations.
• Understanding how these properties modulate channel function is crucial for deciphering protein-lipid interactions.

Purpose of the Study:

• To investigate the relative importance of curvature and elasticity in altering bilayer properties and modulating channel function.
• To examine the effects of specific amphiphiles (Triton X-100, reduced Triton X-100, capsaicin) on alamethicin and gramicidin channel function.

Main Methods:

• Utilized micelle-forming amphiphiles and HII lipid phase promoters to perturb bilayer properties.
• Investigated changes in gramicidin channel appearance rates, lifetimes, and conductance states of alamethicin channels.
• Employed gramicidin channels of varying lengths to probe bilayer elasticity changes.

Main Results:

• Amphiphile addition increased gramicidin channel rates and lifetimes and stabilized higher conductance states in alamethicin channels, irrespective of curvature change direction.
• Modulating intrinsic curvature via phospholipid head group interactions stabilized alamethicin channels but destabilized gramicidin channels.
• Amphiphile adsorption increased bilayer elasticity, while head group alterations did not.

Conclusions:

• Both alamethicin and gramicidin channels are modulated by lipid bilayer properties, with distinct responses to changes in curvature and elasticity.
• Negative curvature stabilizes alamethicin channels but destabilizes gramicidin channels.
• Increased bilayer elasticity stabilizes both channel types, and its energetic impact often outweighs that of curvature changes.