title: Randomly organized lipids and marginally stable proteins: a coupling of weak interactions to optimize membrane signaling.
abstract: Eukaryotic lipids in a bilayer are dominated by weak cooperative interactions. These interactions impart highly dynamic and pliable properties to the membrane. C2 domain-containing proteins in the membrane also interact weakly and cooperatively giving rise to a high degree of conformational plasticity. We propose that this feature of weak energetics and plasticity shared by lipids and C2 domain-containing proteins enhance a cell's ability to transduce information across the membrane. We explored this hypothesis using information theory to assess the information storage capacity of model and mast cell membranes, as well as differential scanning calorimetry, carboxyfluorescein release assays, and tryptophan fluorescence to assess protein and membrane stability. The distribution of lipids in mast cell membranes encoded 5.6-5.8bits of information. More information resided in the acyl chains than the head groups and in the inner leaflet of the plasma membrane than the outer leaflet. When the lipid composition and information content of model membranes were varied, the associated C2 domains underwent large changes in stability and denaturation profile. The C2 domain-containing proteins are therefore acutely sensitive to the composition and information content of their associated lipids. Together, these findings suggest that the maximum flow of signaling information through the membrane and into the cell is optimized by the cooperation of near-random distributions of membrane lipids and proteins. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA; Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Rice
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Mahling
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Fealey
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA.
authors.forename: Anika
authors.initials: A
authors.lastname: Rannikko
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Dunleavy
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA.
authors.forename: Troy
authors.initials: T
authors.lastname: Hendrickson
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA.
authors.forename: K Jean
authors.initials: KJ
authors.lastname: Lohese
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA.
authors.forename: Spencer
authors.initials: S
authors.lastname: Kruggel
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA.
authors.forename: Hillary
authors.initials: H
authors.lastname: Heiling
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Harren
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
authors.forename: R Bryan
authors.initials: RB
authors.lastname: Sutton
authors.affiliation: Department of Biology, University of Minnesota Duluth, Duluth, MN, USA.
authors.forename: John
authors.initials: J
authors.lastname: Pastor
authors.affiliation: Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA. Electronic address: ahinderl@d.umn.edu.
authors.forename: Anne
authors.initials: A
authors.lastname: Hinderliter
mesh_terms: D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008407:Mast Cells / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
chemical_list: D008051:Lipid Bilayers; D008055:Lipids; D008565:Membrane Proteins; D010713:Phosphatidylcholines
keywords: C2 domain; Disorder; Information theory; Membrane domain; Signaling