title: Effects of ion interactions with a cholesterol-rich bilayer.
abstract: Previous molecular dynamics (MD) simulations of ion-lipid interactions have focused on pure phospholipid bilayers. Many functional microdomains in membranes have a complex composition of cholesterol and phospholipids. Here, we reveal the distinctiveness of the interactions and the effects of the ions on a cholesterol-rich bilayer by performing MD simulations of a cholesterol-rich bilayer with a Na(+)/K(+) mixture or a Na(+)/K(+)/Ca(2+)/Mg(2+) mixture. The simulations reveal that Ca(2+) maintains its dominant role in the interaction with the cholesterol-rich bilayer, but the binding affinity of Mg(2+) to the cholesterol-rich bilayer is even weaker than the affinities of Na(+) and K(+), whereas its interaction with pure phospholipid bilayers is strong and is only slightly weaker than that of Ca(2+). Additionally, it was found that the presence of additional divalent cations induces the headgroups of phospholipids to be more perpendicular to the membrane surface, reducing the lateral movement of lipids and slightly altering the ordering and packing of the cholesterol-rich bilayer, different from divalent cations, which strongly influence that ordering and packing of pure phospholipid bilayers. Therefore, this study indicates that cholesterol in the membrane could affect the interactions between membrane and cations. The findings could be helpful in understanding the biological processes relevant to regulation of cations in cholesterol-rich regions.
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Lingxue
authors.initials: L
authors.lastname: Mao
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Qiansen
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China; Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address: hljiang@simm.ac.cn.
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address: hyyang@simm.ac.cn.
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Yang
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002413:Cations, Divalent / Q000737:chemistry / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002413:Cations, Divalent; D008051:Lipid Bilayers; D010743:Phospholipids; D002784:Cholesterol; D008274:Magnesium; D002118:Calcium
keywords: Binding affinity; Cholesterol-rich bilayer; Ion mixture; Molecular dynamics