Hydrophobic Matching Between Phospholipid Bilayers and Helical Peptides Affects the Memrbane Affinity of Sterols

Abstract

The lateral organization of cell membranes is important for several cellular functions including signaling and membrane trafficking. In addition pathogen uptake and influenza virus budding is associated with sphingolipid and cholesterol enriched lateral membrane domains. The lateral structure of membranes is in part controlled by lipid self-organization, but it is becoming increasingly clear that also membrane proteins can play an active role in the maintenance of the lateral structure. Cholesterol is thought to have an important role in lateral organization of eukaryotic cell membranes. As cholesterol also has been implicated to take part in the sorting of cellular transmembrane proteins it is a good starting point to determine how transmembrane proteins influence the lateral sorting of cholesterol in phospholipid bilayers. Insight into this can be obtained by studying how cholesterol interacts with bilayer membranes of different composition in the presence of different transmembrane peptides, mimicking the transmembrane helices of proteins. By measuring the equilibrium partitioning of the fluorescent cholesterol analogue cholestatrienol (CTL) between large unilamellar vesicles and methyl-beta-cyclodextrin the effect of hydrophobic matching on the affinity of sterols for phospholipid bilayers was determined. The results showed that increasing positive mismatch led to higher affinity of the sterol for the bilayers. This suggests that hydrophobic matching could affect the lateral organization of cholesterol in cell membranes and have an important role especially in membrane trafficking.