Biophysical Society Thematic Meeting | Ascona, Switzerland

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

Poster Abstracts

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.

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