Unquenchable
Surface Potential Dramatically Enhances
Cu<sup>2+</sup> Binding to Phosphatidylserine Lipids
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Abstract
Herein,
the apparent equilibrium dissociation constant, <i>K</i><sub>Dapp</sub>, between Cu<sup>2+</sup> and 1-palmitoyl-2-oleoyl-<i>sn-</i>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 <i>K</i><sub>Dapp</sub> for Cu<sup>2+</sup> 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<sup>2+</sup> 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<sup>2+</sup> within the double layer above the membrane was largely responsible
for the tightening. Unlike the binding of other divalent metal ions
such as Ca<sup>2+</sup> and Mg<sup>2+</sup> to PS, Cu<sup>2+</sup> binding does not alter the net negative charge on the membrane as
the Cu(PS)<sub>2</sub> complex forms. As such, the Cu<sup>2+</sup> 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<sup>2+</sup>–PS binding in cell membranes, which may be relevant to biological
processes such as amyloid-β peptide toxicity and lipid oxidation