Absorption of Phosphonium Cations and Dications into a Hydrated POPC Phospholipid Bilayer: A Computational Study

Molecular dynamics (MD) based on an empirical force field is applied to investigate the effect of phosphonium cations ([P6,6,6,6]+) and geminal dications ([DxC10]2+) inserted at T = 300 K into the hydration layer separating planar POPC phospholipid bilayers. Up to high concentration, nearly every added cation and dication becomes absorbed into the lipid phase. Absorption takes place during several microseconds and is virtually irreversible. The neutralizing counterions ([Cl]-, in the present simulation) remain dissolved in water, giving origin to the charge separation and the strong electrostatic double layer at the water/lipid interface. Incorporation of cations and dications changes the properties of the lipid bilayer such as diffusion, viscosity, and the electrostatic pattern. At high ionic concentration, the bilayer acquires a long-wavelength standing undulation, corresponding to a change of phase from fluid planar to ripple. All these changes are potentially able to affect processes relevant in the context of cell biology. The major difference between cations and dications concerns the kinetics of absorption, which takes place nearly two times faster in the [P6,6,6,6]+ case, and for [DxC10]2+ dications displays a marked separation into two-stages, corresponding to the easy absorption of the first phosphonium head of the dication and the somewhat more activated absorption of the second phosphonium head of each dication.

Automated summary

Molecular dynamics simulations were used to investigate the effects of phosphonium cations and geminal dications on the hydration layer of phospholipid bilayers. The results showed that at high concentration, the ions became absorbed into the lipid phase, leading to changes in the properties of the lipid bilayer. The absorption kinetics were found to be different for cations and dications, with cations being absorbed faster than dications.