Aspirin locally disrupts the liquid-ordered phase

Area of Science:

• Membrane biophysics
• Lipid dynamics
• Pharmacological effects on membranes

Background:

• Lipid membrane structure and dynamics are crucial for cellular functions like molecule diffusion and domain formation.
• Cholesterol-rich lipid domains (rafts) influence membrane properties and interactions.
• Collective lipid tail fluctuations impact membrane permeability and domain organization.

Purpose of the Study:

• To investigate the effect of aspirin (acetylsalicylic acid, ASA) on the local structure and dynamics of dimyristoylphosphocholine (DMPC) and cholesterol lipid membranes.
• To understand how ASA interacts with and potentially modifies cholesterol-rich lipid domains.
• To elucidate the molecular mechanisms by which ASA influences membrane collective dynamics.

Main Methods:

• Coherent inelastic neutron scattering (CINS) experiments to probe membrane dynamics.
• Molecular dynamics (MD) simulations to model lipid-cholesterol-ASA interactions.
• Analysis of lipid tail collective fluctuations and domain organization.

Main Results:

• ASA binds to liquid-ordered, raft-like domains within the DMPC-cholesterol membranes.
• ASA binding disturbs the organization of these lipid domains.
• ASA dampens collective lipid tail fluctuations and suppresses cholesterol's ordering effect through hydrogen bonding.
• ASA forms 'superfluid' complexes with lipids, enabling lateral organization into superlattices.

Conclusions:

• Aspirin (ASA) actively modulates the structure and dynamics of lipid membranes, particularly within cholesterol-rich domains.
• The interaction of ASA with lipid membranes involves hydrogen bonding, leading to altered domain organization and suppressed collective fluctuations.
• ASA's ability to form ordered complexes and counteract cholesterol's effects suggests a novel mechanism for its influence on membrane properties.