Membrane lipid bilayers, long viewed as homogenous solvents for membrane proteins ( 1 ), actually show lateral heterogeneity at two different scales, transient nanometric assemblies in "lipid rafts" ( 2-6 ) versus submicrometric/ mesoscale domains evidenced not only on artifi cial vesicles ( 3, 7-11 ) but also on living cells ( 12-23 ). The major structural lipids at the mammalian plasma membrane (PM) are: i ) glycerophospholipids, hereafter represented by phosphatidylcholine (PC); ii ) sphingolipids (SLs) including SM and glycosphingolipids (GSLs), an heterogeneous family from the simple glucosylceramide (GlcCer) to complex monosialotetrahexosylganglioside (GM1) (for a review, see Ref. 24 ); and iii ) cholesterol, a crucial fl uidity regulator without a protruding polar head. The wedgelike shapes of SLs and cholesterol allow them to come in very close apposition via van der Waals forces and this proximity is proposed to account for their spontaneous clustering into lipid rafts ( 25 ). This nanometric short-lived lateral asymmetry led to the fi rst revision of the original Singer-Nicolson model ( 2, 26 ).In addition, compartmentation of polar lipids into stable submicrometric PM domains in living cells was originally

OO9S/t6ThL99Li6L9O 9zz .!oA 3IdS/ Z9 Downloaded From: http://proceedings.spiedigitallibrary.org/ on 06/28/2016 Terms of Use: http://spiedigitallibrary.org/ss/TermsOfUse.aspx 10. K. Egbaria, C. Ramachandran, N. Weiner, "Topical application of liposomally entrapped ciclosporin evaluated by in vitro diffusion studies with human skin," Skin Pharmacol., 4, 21-28, 1991. SPIE Vol. 2328 /89 Downloaded From: http://proceedings.spiedigitallibrary.org/ on 06/28/2016 Terms of Use: http://spiedigitallibrary.org/ss/TermsOfUse.aspx