title: Lipid packing drives the segregation of transmembrane helices into disordered lipid domains in model membranes.
abstract: Cell membranes are comprised of multicomponent lipid and protein mixtures that exhibit a complex partitioning behavior. Regions of structural and compositional heterogeneity play a major role in the sorting and self-assembly of proteins, and their clustering into higher-order oligomers. Here, we use computer simulations and optical microscopy to study the sorting of transmembrane helices into the liquid-disordered domains of phase-separated model membranes, irrespective of peptide-lipid hydrophobic mismatch. Free energy calculations show that the enthalpic contribution due to the packing of the lipids drives the lateral sorting of the helices. Hydrophobic mismatch regulates the clustering into either small dynamic or large static aggregates. These results reveal important molecular driving forces for the lateral organization and self-assembly of transmembrane helices in heterogeneous model membranes, with implications for the formation of functional protein complexes in real cells.
authors.affiliation: Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands. l.schafer@rug.nl
authors.forename: Lars V
authors.initials: LV
authors.lastname: Schäfer
authors.forename: Djurre H
authors.initials: DH
authors.lastname: de Jong
authors.forename: Andrea
authors.initials: A
authors.lastname: Holt
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Rzepiela
authors.forename: Alex H
authors.initials: AH
authors.lastname: de Vries
authors.forename: Bert
authors.initials: B
authors.lastname: Poolman
authors.forename: J Antoinette
authors.initials: JA
authors.lastname: Killian
authors.forename: Siewert J
authors.initials: SJ
authors.lastname: Marrink
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D018613:Microscopy, Confocal; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008563:Membrane Lipids; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; C002448:1,2-linoleoylphosphatidylcholine; D002784:Cholesterol