Lipid phase separation in phospholipid bilayers and monolayers modeling the plasma membrane

It is postulated that biological membrane lipids are heterogeneously distri buted into lipid microdomains. Recent evidence indicates that docosahexaeno ic acid-containing phospholipids may be involved in biologically important lipid phase separations. Here we investigate the elastic and thermal proper ties of a model plasma membrane composed of egg sphingomyelin (SM), cholest erol and 1-stearoyl-2-docosahexaenoyl-sn-glycerophosphoethanolamine (SDPE). Two techniques are employed, pressure-area isotherms on monolayers to exam ine condensation and interfacial elasticity behavior, and differential scan ning calorimetry (DSC) on bilayers to evaluate phase separations. Significa nt levels of condensation are observed for mixtures of SM and cholesterol. Surface elasticity measurements indicate that cholesterol decreases and SDP E increases the in-plane elasticity of SM monolayers. At X-SDPE greater tha n or equal to 0.15 in SM, a more horizontal region emerges in the pressure- area isotherms indicating 'squeeze out' of SDPE from the monolayers. Additi on of cholesterol to equimolar amounts of SM and SDPE further increases the amount of 'squeeze out', supporting the concept of phase separation into a cholesterol- and SM-rich liquid ordered phase and a SDPE-rich liquid disor dered phase. This conclusion is corroborated by DSC studies where as little as X-Chol = 0.0025 induces a phase separation between the two lipids. (C) 2001 Published by Elsevier Science B.V.