title: Intermolecular Headgroup Interaction and Hydration as Driving Forces for Lipid Transmembrane Asymmetry.
abstract: Variations between the inner and outer leaflets of cell membranes are crucial for cell functioning and signaling, drug-membrane interactions, and the formation of lipid domains. Transmembrane asymmetry can in principle be comprised of an asymmetric charge distribution, differences in hydration, specific headgroup/H-bonding interactions, or a difference in the number of lipids per leaflet. Here, we characterize the transmembrane asymmetry of small unilamellar liposomes consisting of zwitterionic and charged lipids in aqueous solution using vibrational sum frequency scattering and second harmonic scattering, label-free methods, specifically sensitive to lipid and water asymmetries. For single component liposomes, transmembrane asymmetry is present for the charge distribution and lipid hydration, but the leaflets are not detectably asymmetric in terms of the number of lipids per leaflet, even though geometrical packing arguments would predict so. Such a lipid transmembrane asymmetry can, however, be induced in binary lipid mixtures under conditions that enable H-bonding interactions between phosphate and amine groups. In this case, the measured asymmetry consists of a different number of lipids in the outer and inner leaflet, a difference in transmembrane headgroup hydration, and a different headgroup orientation for the interacting phosphate groups.
authors.affiliation: Laboratory for Fundamental BioPhotonics (LBP), Institute of Bioengineering (IBI), and Institute of Materials Science (IMX), School of Engineering (STI), and Lausanne Centre for Ultrafast Science (LACUS), École Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Smolentsev
authors.affiliation: Laboratory for Fundamental BioPhotonics (LBP), Institute of Bioengineering (IBI), and Institute of Materials Science (IMX), School of Engineering (STI), and Lausanne Centre for Ultrafast Science (LACUS), École Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Lütgebaucks
authors.affiliation: Laboratory for Fundamental BioPhotonics (LBP), Institute of Bioengineering (IBI), and Institute of Materials Science (IMX), School of Engineering (STI), and Lausanne Centre for Ultrafast Science (LACUS), École Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors.forename: Halil I
authors.initials: HI
authors.lastname: Okur
authors.affiliation: Laboratory for Fundamental BioPhotonics (LBP), Institute of Bioengineering (IBI), and Institute of Materials Science (IMX), School of Engineering (STI), and Lausanne Centre for Ultrafast Science (LACUS), École Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors.forename: Alex G F
authors.initials: AG
authors.lastname: de Beer
authors.affiliation: Laboratory for Fundamental BioPhotonics (LBP), Institute of Bioengineering (IBI), and Institute of Materials Science (IMX), School of Engineering (STI), and Lausanne Centre for Ultrafast Science (LACUS), École Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Roke
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D053835:Unilamellar Liposomes / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D008051:Lipid Bilayers; D053835:Unilamellar Liposomes; D014867:Water