Unquenchable Surface Potential Dramatically Enhances Cu(2+) Binding to Phosphatidylserine Lipids

• Published in: Journal of the American Chemical Society 2015-06, Vol.137 (24), p.7785
• Main Authors: Cong, Xiao, Poyton, Matthew F, Baxter, Alexis J, Pullanchery, Saranya, Cremer, Paul S
• Format: Article
• Language: English
• Subjects: Cations, Divalent - metabolism; Copper - metabolism; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Phosphatidylserines - chemistry; Phosphatidylserines - metabolism; Static Electricity; Surface Properties
• ISSN: 1520-5126
• DOI: 10.1021/jacs.5b03313

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.