Investigating Al3+ effects on lipid membrane diffusion and rigidity: FRAP and Molecular Dynamics Simulations
Aluminum is the most common metal in the earth's crust, yet the ion Al3+ is a well-known neurotoxin. It derives toxicity from the structural changes it induces in lipid membranes upon binding, including increasing bilayer rigidity, facilitating vesicle fusion, and inducing vesicle rupture. However, the mechanism for these processes is not well understood. We implement Fluorescence Recovery After Photobleaching (FRAP) and Molecular Dynamics (MD) simulations to better understand the mechanism of the system. We provide a quantitative analysis of the effect of increasing Al3+ concentration on membrane diffusion in both zwitterionic and anionic membranes, as measured by both FRAP and MD. We also investigate the coordination structure of Al3+ with phosphatidylcholine lipid head groups, and report Al3+ coordination to the phosphate groups and acyl chain carbonyl groups. Our results indicate that addition of Al3+ to membranes causes an overall increase in rigidity and decrease in diffusion for zwitterionic membranes, and possibly a transition to gel phase in anionic membranes. Understanding Al3+-membrane interactions is important for a better understanding of the mechanism of aluminum toxicity in biological systems.