The lipid charge density at the bilayer surface modulates the effects of melittin on membranes

Area of Science:

• Biophysics
• Membrane Biophysics
• Biochemistry

Background:

• Melittin, a peptide from bee venom, is known to interact with lipid bilayers.
• The behavior of phospholipids like dimyristoylphosphatidic acid (DMPA) in membranes is crucial for understanding cellular processes.
• Investigating peptide-lipid interactions provides insights into membrane structure and dynamics.

Purpose of the Study:

• To investigate the influence of melittin on DMPA membrane systems at different pH values (4.2 and 8.2).
• To elucidate the morphological and dynamic changes induced by melittin in DMPA membranes.
• To understand the molecular mechanisms of melittin-lipid interactions.

Main Methods:

• Solid-state 31P and 2H Nuclear Magnetic Resonance (NMR) spectroscopy were employed.
• Experiments were conducted as a function of temperature and peptide concentration.
• Analysis focused on lipid acyl chain dynamics and membrane phase behavior.

Main Results:

• Melittin induced greater morphological changes in fluid-phase DMPA systems, with more pronounced effects at pH 4.2.
• At pH 8.2, melittin interactions with DMPA showed similarities to melittin interactions with phosphatidylcholine (PC) systems.
• At pH 4.2 and high temperatures, a lipid-to-peptide ratio of 30 transformed the system into isotropic inverted micelles, transitioning to a hexagonal phase upon cooling.

Conclusions:

• Melittin significantly impacts DMPA membrane morphology, with pH-dependent effects.
• The study reveals specific molecular interactions, including charge neutralization at the lipid-peptide interface at pH 8.2.
• Melittin can induce distinct phase transitions in DMPA systems, highlighting its potent membrane-disrupting capabilities.