Lipid Structure Determines the Differential Impact of Single Metal Additions and Binary Mixtures of Manganese, Calcium and Magnesium on Membrane Fluidity and Liposome Size

Abstract

Unilamellar vesicles of the biologically relevant lipids phosphatidic acid (PA) and phosphatidylserine (PS) with fully saturated (DM-) or partly unsaturated (PO-) acyl side chains were exposed to Ca, Mn and Mg in single metal additions; in equimolar mixtures or by sequential additions of one metal at a time. Laurdan generalized polarization measured the membrane fluidity, while dynamic light scattering reported liposome size changes complemented by zeta potential. All metals induced membrane rigidity and increased liposome sizes across all systems. Mn had the strongest effect overall, but Mg was comparable for DMPS. Lipid side chain architecture was important as GP values for binary mixtures were higher than expected from the sum of values for single additions added to POPS but smaller for DMPS. Sequential additions were predominantly different for Ca:Mg mixtures. Mn induced the strongest increase of liposome size in saturated lipids whereas Ca effects dominated unsaturated matrices. Binary additions induced larger sizes than the sum of single additions for POPS, but much lower changes in DMPA. The order of addition was relevant for PS systems. Thus, lipid structure determines metal effects, but their impact is modulated by other ions. Thus, metal effects may differ with the local lipid architecture and metal concentrations within cells.

Gadolinium Effects on Liposome Fluidity and Size Depend on the Headgroup and Side Chain Structure of Key Mammalian Brain Lipids

“…Enhanced demixing and tighter packed domains may facilitate metal complexation [ 46 ]. This agrees with the PC results above but also with previous reports showing much stronger effects of Mn 2+ , Cd 2+ , Ni 2+ , and Co 2+ on saturated over monounsaturated negatively charged lipids [ 23 , 25 , 28 ].…”

“…We previously compared the impact of Gd on membrane fluidity with the effects of other toxic metals (Pb 2+ , Cd 2+ , Ni 2+ ) or essential/non-toxic metals (Ca 2+ , Mn 2+ , Co 2+ ), and Gd 3+ induced the strongest decrease in fluidity [ 6 ]. Like other cations [ 23 ], Gd 3+ targeted negatively charged lipids and preferred saturated over unsaturated membranes [ 6 ]. In contrast to the others, except for Pb 2+ [ 6 ], Gd 3+ was able to induce rigidity in sphingomyelin (SM)-containing membranes as well as complex brain lipid extracts [ 6 ].…”

“…Positively charged ions have been shown to promote liposome aggregation [ 25 ] as well as membrane fusion [ 23 ]. Previous data indicated a stronger potential of Gd 3+ to increase the size of liposomes composed of polar brain lipid extract to a greater extent than liposomes composed of partly unsaturated and negatively charged phosphatidylserine (PS) [ 6 ], at the same metal concentration.…”

Salt-Induced Adsorption and Rupture of Liposomes on Microplastics

“…Figure F summarizes the leakage rates calculated from the slope of the initial 10 min of leakage kinetics. Ca 2+ is slightly more efficient than Mg 2+ in facilitating liposome rupture on the PP microplastics, which can be explained by better bonding affinity of Ca 2+ for phosphate of lipids than that of Mg 2+ . , Considering the Debye lengths ( k –1 ) of the divalent ions (e.g., k –1 ≃ 1.62 nm for 2.5 mM Mg 2+ and Ca 2+ in 10 mM HEPES) and the monovalent ions ( k –1 ≃ 0.47 nm for 200 mM Na + ), divalent metals have additional roles beyond simple charge screening. It is possible that they can act as a salt bridge to directly interact with negatively charged groups on both the microplastics and liposomes.…”