Unquenchable Surface Potential Dramatically Enhances Cu²⁺ Binding to Phosphatidylserine Lipids

Herein, the apparent equilibrium dissociation constant, <i>K</i>_Dapp, between Cu²⁺ 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>_Dapp for Cu²⁺ 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 Cu²⁺ bound bivalently to POPS at higher PS concentrations, this was not the dominant factor in increasing the binding affinity. Rather, the higher concentration of Cu²⁺ within the double layer above the membrane was largely responsible for the tightening. Unlike the binding of other divalent metal ions such as Ca²⁺ and Mg²⁺ to PS, Cu²⁺ binding does not alter the net negative charge on the membrane as the Cu­(PS)₂ complex forms. As such, the Cu²⁺ 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 Cu²⁺–PS binding in cell membranes, which may be relevant to biological processes such as amyloid-β peptide toxicity and lipid oxidation

What Is the Preferred Conformation of Phosphatidylserine–Copper(II) Complexes? A Combined Theoretical and Experimental Investigation

Phosphatidylserine (PS) has previously been found to bind Cu²⁺ in a ratio of 1 Cu²⁺ ion per 2 PS lipids to form a complex with an apparent dissociation constant that can be as low as picomolar. While the affinity of Cu²⁺ for lipid membranes containing PS lipids has been well characterized, the structural details of the Cu–PS₂ complex have not yet been reported. Coordinating to one amine and one carboxylate moiety on two separate PS lipids, the Cu–PS₂ complex is unique among ion–lipid complexes in its ability to adopt both <i>cis</i> and <i>trans</i> conformations. Herein, we determine which stereoisomer of the Cu–PS₂ complex is favored in lipid bilayers using density functional theory calculations and electron paramagnetic resonance experiments. It was determined that a conformation in which the nitrogen centers are <i>cis</i> to each other is the preferred binding geometry. This is in contrast to the complex formed when two glycine molecules bind to Cu²⁺ in bulk solution, where the <i>cis</i> and <i>trans</i> isomers exist in equilibrium, indicating that the lipid environment has a significant steric effect on the Cu²⁺ binding conformation. These findings are relevant for understanding lipid oxidation caused by Cu²⁺ binding to lipid membrane surfaces and will help us understand how ion binding to lipid membranes can affect their physical properties

Plexcitons: The Role of Oscillator Strengths and Spectral Widths in Determining Strong Coupling

Strong coupling interactions between plasmon and exciton-based excitations have been proposed to be useful in the design of optoelectronic systems. However, the role of various optical parameters dictating the plasmon-exciton (plexciton) interactions is less understood. Herein, we propose an inequality for achieving strong coupling between plasmons and excitons through appropriate variation of their oscillator strengths and spectral widths. These aspects are found to be consistent with experiments on two sets of free-standing plexcitonic systems obtained by (i) linking fluorescein isothiocyanate on Ag nanoparticles of varying sizes through silane coupling and (ii) electrostatic binding of cyanine dyes on polystyrenesulfonate-coated Au nanorods of varying aspect ratios. Being covalently linked on Ag nanoparticles, fluorescein isothiocyanate remains in monomeric state, and its high oscillator strength and narrow spectral width enable us to approach the strong coupling limit. In contrast, in the presence of polystyrenesulfonate, monomeric forms of cyanine dyes exist in equilibrium with their aggregates: Coupling is not observed for monomers and H-aggregates whose optical parameters are unfavorable. The large aggregation number, narrow spectral width, and extremely high oscillator strength of J-aggregates of cyanines permit effective delocalization of excitons along the linear assembly of chromophores, which in turn leads to efficient coupling with the plasmons. Further, the results obtained from experiments and theoretical models are jointly employed to describe the plexcitonic states, estimate the coupling strengths, and rationalize the dispersion curves. The experimental results and the theoretical analysis presented here portray a way forward to the rational design of plexcitonic systems attaining the strong coupling limits