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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
79
17-POS
Board 9
Modulation of Membrane Viscosity by Integral Membrane Proteins
Marie Olsinova, Lukasz Cwiklik, Piotr Jurkiewicz, Jan Sykora, Martin Hof.
Marek Cebecauer
,
J. Heyrovsky Institute of Physical Chemistry, Prague, Czech Republic.
Integral proteins of the plasma membrane are involved in a variety of biological processes. Such
proteins frequently form transient nanoclusters with poorly understood function. Transmembrane
domains (TMDs) form the closest contact of integral proteins with surrounding lipids, potentially
influencing their properties. We have investigated LW21, an artificially-designed,
transmembrane helical peptide with amino acid sequence
GLLDSKKWWLLLLLLLLALLLLLLLLWWKKFSRS in unilamellar vesicles composed of
mono-unsaturated lipid, dioleylphosphatidylcholine (DOPC). Mobility of peptides and lipids
(tracers) was determined in the absence and presence of cholesterol. We observed that the
presence of low and physiological concentrations of LW21 peptide (1-3 mol%) caused
significant reduction in mobility of both, lipids and peptides. This effect was even more
pronounced in the presence of 25 mol% cholesterol. Interestingly, indistinguishable diffusion of
lipids and peptides was measured in the presence of cholesterol, supporting transbilayer effect of
cholesterol in lipid membranes. Our observations cannot be explained solely by currently
preferred models of membrane organisation. No peptide aggregation, lipid segregation or
anomalous diffusion due to obstacles were detected. LW21 exhibits no hydrophobic mismatch in
DOPC membranes, irrespective of the presence of cholesterol. Rather, our data indicate that the
peptide increases local microviscosity in lipid membranes. We support this prediction with
quantitative MD simulations and experimentally, showing that the peptide increases rigidity of
the membrane at the level of phospholipid carbonyl groups, as well as acyl chains. In summary,
we re-emphasise the impact of integral membrane proteins on the mobility of membrane
components and propose a simple model how dense protein clusters may locally alter membrane
properties.