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

Area of Science:

• Biochemistry
• Biophysics
• Membrane Biology

Background:

• Copper ions (Cu2+) play crucial roles in biological systems.
• Phospholipids, particularly phosphatidylserine (PS), are key components of cell membranes.
• Understanding metal-ion interactions with lipids is vital for cellular function.

Purpose of the Study:

• To quantify the apparent equilibrium dissociation constant (K(Dapp)) for Cu2+ binding to PS in supported lipid bilayers (SLBs).
• To investigate the effect of PS density on Cu2+ binding affinity.
• To elucidate the mechanism behind enhanced Cu2+ binding affinity.

Main Methods:

• Utilized supported lipid bilayers (SLBs) with varying concentrations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS).
• Measured the apparent equilibrium dissociation constant (K(Dapp)) for Cu2+ binding as a function of PS concentration.
• Analyzed the contribution of electrostatic effects and complex formation to binding affinity.

Main Results:

• Cu2+ binding affinity to PS-containing SLBs increased dramatically (17,000-fold) as PS density rose from 1.0 to 20 mol %.
• K(Dapp) decreased from 110 nM to 6.4 pM with increasing PS density.
• Enhanced binding was primarily due to increased Cu2+ concentration in the membrane's double layer, not bivalent binding.

Conclusions:

• Cu2+ binding to PS is highly sensitive to PS density in membranes.
• The amplification of Cu2+ concentration in the double layer significantly boosts binding affinity.
• Findings offer insights into Cu2+-PS interactions in cell membranes, relevant to amyloid-β toxicity and lipid oxidation.