title: Crosslinking a lipid raft component triggers liquid ordered-liquid disordered phase separation in model plasma membranes.
abstract: The mechanisms by which a cell uses and adapts its functional membrane organization are poorly understood and are the subject of ongoing investigation and discussion. Here, we study one proposed mechanism: the crosslinking of membrane components. In immune cell signaling (and other membrane-associated processes), a small change in the clustering of specific membrane proteins can lead to large-scale reorganizations that involve numerous other membrane components. We have investigated the large-scale physical effect of crosslinking a minor membrane component, the ganglioside GM1, in simple lipid models of the plasma membrane containing sphingomyelin, cholesterol, and phosphatidylcholine. We observe that crosslinking GM1 can cause uniform membranes to phase-separate into large, coexistent liquid ordered and liquid disordered membrane domains. We also find that this lipid separation causes a dramatic redistribution of a transmembrane peptide, consistent with a raft model of membrane organization. These experiments demonstrate a mechanism that could contribute to the effects of crosslinking observed in cellular processes: Domains induced by clustering a small number of proteins or lipids might rapidly reorganize many other membrane proteins.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Hammond
authors.forename: F A
authors.initials: FA
authors.lastname: Heberle
authors.forename: T
authors.initials: T
authors.lastname: Baumgart
authors.forename: D
authors.initials: D
authors.lastname: Holowka
authors.forename: B
authors.initials: B
authors.lastname: Baird
authors.forename: G W
authors.initials: GW
authors.lastname: Feigenson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism*; D005453:Fluorescence; D005677:G(M1) Ganglioside / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013696:Temperature
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003432:Cross-Linking Reagents; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D005677:G(M1) Ganglioside