Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Poster Abstracts

43-POS Board 22 Effect of Hydrocarbons and Alcohols on Lipid Phase Separation – A Simulation Perspective Jonathan Barnoud 1 , Giulia Rossi 2 , Siewert-Jan Marrink 1 , Luca Monticelli 3 . 3 CNRS, Lyon, France. 1 University of Groningen, Groningen, Netherlands, 2 University of Genoa, Genoa, Italy, Cell membranes have a complex lateral organization featuring domains with distinct composition, also known as rafts, which play an essential role in cellular processes such as signal transduction and protein trafficking. In vivo, perturbation of membrane domains (e.g., by drugs and anesthetics) has major effects on the activity of raft-associated proteins and on signaling pathways [1]. In live cells, membrane domains are difficult to characterize because of their small size and highly dynamic nature, so model membranes are often used to understand the driving forces of membrane lateral organization. Studies in model membranes have shown that some lipophilic compounds can alter membrane domains, but it is not clear which chemical and physical properties determine domain perturbation. The mechanisms of domain stabilization and destabilization are also unknown. Here we describe the effect of hydrocarbons and alcohols of different chain length on the lateral organization of phase-separated model membranes consisting of saturated and unsaturated phospholipids and cholesterol [2]. Using molecular simulations at the coarse-grained level, we predict that aliphatic compounds promote lipid mixing by distributing at the interface between liquid-ordered and liquid-disordered domains. Long-chain alcohols also destabilize phase separation, although they do not act as linactants. Short-chain alcohols, instead, appear to have little effect on membrane lateral organization, at physiologically relevant concentrations. We predict that relatively small concentrations of hydrophobic species can have a broad impact on domain stability in model systems, which suggests possible mechanisms of action for hydrophobic pollutants in vivo.

References [1] K Simons, R Ehehalt, J Clin Invest (2002) 110, 597–603 [2] J Barnoud, G Rossi, SJ Marrink, L Monticelli, PLoS Comp Biol. (2014) 10, e1003873

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