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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
66
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