title: Unquenchable Surface Potential Dramatically Enhances Cu(2+) Binding to Phosphatidylserine Lipids.
abstract: Herein, the apparent equilibrium dissociation constant, K(Dapp), between Cu(2+) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS), a negatively charged phospholipid, was measured as a function of PS concentrations in supported lipid bilayers (SLBs). The results indicated that K(Dapp) for Cu(2+) binding to PS-containing SLBs was enhanced by a factor of 17,000 from 110 nM to 6.4 pM as the PS density in the membrane was increased from 1.0 to 20 mol %. Although Cu(2+) bound bivalently to POPS at higher PS concentrations, this was not the dominant factor in increasing the binding affinity. Rather, the higher concentration of Cu(2+) within the double layer above the membrane was largely responsible for the tightening. Unlike the binding of other divalent metal ions such as Ca(2+) and Mg(2+) to PS, Cu(2+) binding does not alter the net negative charge on the membrane as the Cu(PS)2 complex forms. As such, the Cu(2+) concentration within the double layer region was greatly amplified relative to its concentration in bulk solution as the PS density was increased. This created a far larger enhancement to the apparent binding affinity than is observed by standard multivalent effects. These findings should help provide an understanding on the extent of Cu(2+)-PS binding in cell membranes, which may be relevant to biological processes such as amyloid-β peptide toxicity and lipid oxidation.
authors.forename: Xiao
authors.initials: X
authors.lastname: Cong
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Poyton
authors.forename: Alexis J
authors.initials: AJ
authors.lastname: Baxter
authors.forename: Saranya
authors.initials: S
authors.lastname: Pullanchery
authors.forename: Paul S
authors.initials: PS
authors.lastname: Cremer
mesh_terms: D002413:Cations, Divalent / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism*; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D002413:Cations, Divalent; D008051:Lipid Bilayers; D010718:Phosphatidylserines; C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; D003300:Copper