Dendritic amphiphiles strongly affect the biophysical properties of DPPC bilayer membranes

Molecular dynamics (MD) simulations were used to gain insight on the molecular interactions in a model biological membrane comprised of a bilayer with DPPC (dipalmitoylphosphotidylcholine) and antimicrobial dendritic amphiphile molecules [RCONHC(CH(2)CH(2)COOH)(3), where R is the saturated hydrocarbon tail (R = n-C(n)H(2n+1)), to be abbreviated as 3CAmn]. This study analyzes different biophysical properties of the equilibrated mixed bilayers, at 300 and 325 K, to determine how the presence of the 3CAmn, in varying concentrations and tail lengths, affects the lipid bilayer. Lipid tail order parameter data, bilayer thickness trends, and qualitative lipid tail tilt observations suggest that a molar ratio of 0.2 3CAm19/DPPC is sufficient to induce a phase transition in the bilayer from gel to liquid crystalline at 300 K. These results also imply that the phase transition temperature of the mixed bilayer decreases upon incorporation of higher concentrations of 3CAm19. Hydrogen bonding takes place between the 3CAmn and DPPC at specific sites, as evidenced by the radial distribution function. Increased hydrogen bonding and the smaller headgroup size of the 3CAmn molecule result in a decrease in the total lateral area with higher concentrations of 3CAm19. Diffusion constants of 3CAmn varied with concentration and tail length; diffusion constants of DPPC and 3CAm19 increased with increasing 3CAm19 concentration at 300 K and shorter 3CAmn tails had higher diffusion constants at both temperatures. These computational studies provide a comprehensive understanding of the biophysical changes to model biological membranes by the association of 3CAmn.