title: The complex nature of calcium cation interactions with phospholipid bilayers.
abstract: Understanding interactions of calcium with lipid membranes at the molecular level is of great importance in light of their involvement in calcium signaling, association of proteins with cellular membranes, and membrane fusion. We quantify these interactions in detail by employing a combination of spectroscopic methods with atomistic molecular dynamics simulations. Namely, time-resolved fluorescent spectroscopy of lipid vesicles and vibrational sum frequency spectroscopy of lipid monolayers are used to characterize local binding sites of calcium in zwitterionic and anionic model lipid assemblies, while dynamic light scattering and zeta potential measurements are employed for macroscopic characterization of lipid vesicles in calcium-containing environments. To gain additional atomic-level information, the experiments are complemented by molecular simulations that utilize an accurate force field for calcium ions with scaled charges effectively accounting for electronic polarization effects. We demonstrate that lipid membranes have substantial calcium-binding capacity, with several types of binding sites present. Significantly, the binding mode depends on calcium concentration with important implications for calcium buffering, synaptic plasticity, and protein-membrane association.
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Dolejškova 3, Prague, 18223, Czech Republic.
authors.forename: Adéla
authors.initials: A
authors.lastname: Melcrová
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Dolejškova 3, Prague, 18223, Czech Republic.
authors.forename: Sarka
authors.initials: S
authors.lastname: Pokorna
authors.affiliation: Department of Chemistry, Pennsylvania State University, University Park, PA 16802, United States.
authors.forename: Saranya
authors.initials: S
authors.lastname: Pullanchery
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, Prague, 16610, Czech Republic.|Institute for Computational Physics, University of Stuttgart, Allmandring 3, Stuttgart, 70569, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Kohagen
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Dolejškova 3, Prague, 18223, Czech Republic.
authors.forename: Piotr
authors.initials: P
authors.lastname: Jurkiewicz
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Dolejškova 3, Prague, 18223, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Hof
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, Prague, 16610, Czech Republic.|Department of Physics, Tampere University of Technology, POB 692, Tampere, FI-33101, Finland.
authors.forename: Pavel
authors.initials: P
authors.lastname: Jungwirth
authors.affiliation: Department of Chemistry, Pennsylvania State University, University Park, PA 16802, United States.|Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, United States.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Cremer
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Dolejškova 3, Prague, 18223, Czech Republic.|Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, Prague, 16610, Czech Republic.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Cwiklik
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002462:Cell Membrane / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D010743:Phospholipids; D002118:Calcium