Structural effects of zinc on phosphatidylserine-containing lipid membranes: kinetic analysis of membrane reorganization

Abstract

The interaction between metal ions and phospholipids plays an essential role in cellular signal transduction, oxidative lipid damage and other biological processes. Herein, we report fluorescence microscopy analysis of the interaction between Zn²⁺ on planar supported lipid bilayers (SLBs), as model membranes. The results show that Zn²⁺ interacts with palmitoyl oleoyl phosphatidylserine (POPS), a negatively charged phospholipid, in palmitoyl oleoyl phosphatidylcholine (POPC) SLBs, which leads to significant structural reorganization of the bilayer. Upon Zn²⁺ binding, the formation of bilayer stacks was observed, which led to the subsequent disruption of the membrane. The kinetics of bilayer stack formation could be described with a characteristic sigmoidal profile and a three-stage mechanism consisting of a lag phase for initial nucleation (formation of stable nuclei), a subsequent exponential phase for growth (growth of nuclei to bilayer stacks) and a final stationary phase was proposed. The lag time reduced in an exponential fashion with increasing Zn²⁺ concentration and the lag phase could be essentially eliminated in SLBs with high POPS content. Moreover, a linear dependency of the apparent first-order rate constant for bilayer stack growth on Zn²⁺ concentration was established. Besides, the equilibrium dissociation constants for Zn²⁺-membrane interaction were calculated and the affinity between Zn²⁺ and SLBs increased with an increase in the POPS content in the membrane. These results have important implications in general understanding of ion-mediated malformations of cell membranes and cell fusion. Also, this work provides an interesting in vitro system for studying metal ions interacting with biomembranes.