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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
101
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.