title: Plasma membranes are poised for activation of raft phase coalescence at physiological temperature.
abstract: Cell membranes are not randomly organized, but rather are populated by fluctuating nanoassemblies of increased translational order termed lipid rafts. This lateral heterogeneity can be biophysically extended because cooling formaldehyde-isolated plasma membrane preparations results in separation into phases similar to the liquid-ordered (Lo) and liquid-disordered (Ld) states seen in model membrane systems [Baumgart T, et al. (2007) Proc Natl Acad Sci USA 104:3165-3170]. In this work we demonstrate that raft clustering, i.e., amplifying underlying raft-based connectivity to a larger scale, makes an analogous capacity accessible at 37 degrees C. In plasma membranes at this temperature, cholera toxin-mediated cross-linking of the raft ganglioside GM1 induced the sterol-dependent emergence of a slower diffusing micrometer-scale phase that was enriched in cholesterol and selectively reorganized the lateral distribution of membrane proteins. Although parallels can be drawn, we argue that this raft coalescence in a complex biological matrix cannot be explained by only those interactions that define Lo formation in model membranes. Under this light, our induction of raft-phase separation suggests that plasma membrane composition is poised for selective and functional raft clustering at physiologically relevant temperature.
authors.affiliation: Max Planck Institute for Molecular Cell Biology and Genetics, Technical University of Dresden, Dresden, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lingwood
authors.forename: Jonas
authors.initials: J
authors.lastname: Ries
authors.forename: Petra
authors.initials: P
authors.lastname: Schwille
authors.forename: Kai
authors.initials: K
authors.lastname: Simons
mesh_terms: D000818:Animals; D002460:Cell Line; D002772:Cholera Toxin / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D004058:Diffusion; D005456:Fluorescent Dyes; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D044367:Phase Transition; D011990:Receptors, Transferrin / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D005456:Fluorescent Dyes; D008024:Ligands; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; D002784:Cholesterol