Aspirin locally disrupts the liquid-ordered phase

• Main Authors: Richard J. Alsop, Sebastian Himbert, Alexander Dhaliwal, Karin Schmalzl, Maikel C. Rheinstädter
• Format: Article
• Language: English
• Published: The Royal Society 2018-01-01
• Series: Royal Society Open Science
• Subjects: lipid membranes; cholesterol; aspirin; liquid-ordered phase; membrane–drug interactions
• Online Access: https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.171710

Local structure and dynamics of lipid membranes play an important role in membrane function. The diffusion of small molecules, the curvature of lipids around a protein and the existence of cholesterol-rich lipid domains (rafts) are examples for the membrane to serve as a functional interface. The collective fluctuations of lipid tails, in particular, are relevant for diffusion of membrane constituents and small molecules in and across membranes, and for structure and formation of membrane domains. We studied the effect of aspirin (acetylsalicylic acid, ASA) on local structure and dynamics of membranes composed of dimyristoylphosphocholine (DMPC) and cholesterol. Aspirin is a common analgesic, but is also used in the treatment of cholesterol. Using coherent inelastic neutron scattering experiments and molecular dynamics (MD) simulations, we present evidence that ASA binds to liquid-ordered, raft-like domains and disturbs domain organization and dampens collective fluctuations. By hydrogen-bonding to lipid molecules, ASA forms ‘superfluid’ complexes with lipid molecules that can organize laterally in superlattices and suppress cholesterol’s ordering effect.