Biophysical Society Thematic Meeting | Ascona, Switzerland

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

Poster Abstracts

21-POS Board 11 Characterization of How Cholesterol´s Affinity for Different Phospholipids Affect Lateral Segregation Oskar Engberg 1 , Victor Hautala 1 , Tomkazu Yasuda 2,3 , Henrike Dehio 1 , Anders Kullberg 1 , Thomas K. Nyholm 1 , Michio Murata 2,3 , J.Peter Slotte 1 . 1 Åbo Akademi University, Turku, Finland, 2 Osaka University, Toyonaka, Osaka, Japan, 3 Japan Science and Technology Agency, Toyonaka, Osaka, Japan. Cholesterol is known to influence lateral domain formation in model membranes, which likely resembles the formation of nanodomains in biological membranes. Lateral segregation is also likely affected by cholesterol’s preference for saturated acyl chains over monounsaturated, and especially polyunsaturated ones. Here we have investigated how cholesterol influenced the lateral segregation of saturated and unsaturated phospholipids (PLs), for which cholesterol had a varying degree of affinity. The formation of ordered domains ((gel or liquid-ordered (lo)) was detected by measuring the fluorescence lifetime of trans-parinaric acid (tPA) in bilayers composed of different unsaturated phosphatidylcholines, and dipalmitoyl-phosphatidylcholine (DPPC) or N-palmitoyl-sphingomyelin (PSM), with and without cholesterol. The tPA experiments showed that cholesterol facilitated lateral segregation, which was dependent on stoichiometry of the mixture of unsaturated and saturated PLs. The facilitated lateral segregation could be explained by correlating the relative affinity of cholesterol for the different PLs in the bilayers. In addition, differential scanning calorimetry (DSC) and 2H nuclear magnetic resonance (NMR) showed that cholesterol increased the thermostability of both the lo-and gel- domains. The acyl order in the lo-domains was increased when the degree of unsaturation was increased in the unsaturated PLs, likely by enriching the ordered domains in saturated lipids and cholesterol. This agreed with the conclusions from the tPA-experiments, and gave insight into how cholesterol facilitated lateral segregation. Our data suggests that knowledge of the relative affinity of cholesterol for the different PLs in a bilayer could predict in which biological membranes cholesterol is most probable to promote lateral domain formation.

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