title: Adaptive lipid packing and bioactivity in membrane domains.
abstract: Lateral compositional and physicochemical heterogeneity is a ubiquitous feature of cellular membranes on various length scales, from molecular assemblies to micrometric domains. Segregated lipid domains of increased local order, referred to as rafts, are believed to be prominent features in eukaryotic plasma membranes; however, their exact nature (i.e. size, lifetime, composition, homogeneity) in live cells remains difficult to define. Here we present evidence that both synthetic and natural plasma membranes assume a wide range of lipid packing states with varying levels of molecular order. These states may be adapted and specifically tuned by cells during active cellular processes, as we show for stimulated insulin secretion. Most importantly, these states regulate both the partitioning of molecules between coexisting domains and the bioactivity of their constituent molecules, which we demonstrate for the ligand binding activity of the glycosphingolipid receptor GM1. These results confirm the complexity and flexibility of lipid-mediated membrane organization and reveal mechanisms by which this flexibility could be functionalized by cells.
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom; Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Erdinc
authors.initials: E
authors.lastname: Sezgin
authors.affiliation: Paul Langerhans Institute Dresden of the Helmholtz Centre Munich at the University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Theresia
authors.initials: T
authors.lastname: Gutmann
authors.affiliation: Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Buhl
authors.affiliation: Paul Langerhans Institute Dresden of the Helmholtz Centre Munich at the University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Ron
authors.initials: R
authors.lastname: Dirkx
authors.affiliation: Paul Langerhans Institute Dresden of the Helmholtz Centre Munich at the University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Michal
authors.initials: M
authors.lastname: Grzybek
authors.affiliation: Paul Langerhans Institute Dresden of the Helmholtz Centre Munich at the University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Ünal
authors.initials: Ü
authors.lastname: Coskun
authors.affiliation: Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany; Paul Langerhans Institute Dresden of the Helmholtz Centre Munich at the University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Michele
authors.initials: M
authors.lastname: Solimena
authors.affiliation: Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Simons
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, Texas, United States of America.
authors.forename: Ilya
authors.initials: I
authors.lastname: Levental
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried-Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Schwille
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000502:physiology*; D006028:Glycosphingolipids / Q000378:metabolism; D008055:Lipids / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism* / Q000502:physiology*; D051381:Rats
chemical_list: D006028:Glycosphingolipids; D008055:Lipids