(38c) Effect of Dendritic Amphiphiles On the Biophysical Properties of Model Biomembranes

Dendritic amphiphile molecules [RCONHC(CH₂CH₂COOH)₃, R = n-C_nH_n+1], possess antimicrobial, antifungal, anti-HIV, and anti-STD properties, giving these molecules great potential in the p­­­harmaceutical industry. In order for dendritic amphiphiles to be considered for pharmaceutical use, the molecules should not disrupt the mammalian cell membrane functionality. Using molecular dynamics simulations, the effects of varying concentration and varying tail lengths of dendritic amphiphiles within a lipid bilayer system were observed at an atomistic level. This project analyzes different biophysical properties of simulated bilayer systems, at equilibrium, to determine how dendritic amphiphiles cause changes to the DPPC lipid bilayer characteristics at 300 K and 325 K, corresponding to temperature below and above, respectively, the lipid bilayer phase transition temperature from gel to liquid-crystalline. From the simulations, we observe that at higher concentrations of amphiphiles in gel-state bilayers (300 K), the lipid tails begin to resemble disordered tails as in the liquid-crystalline state. Hydrogen bonding takes place between the amphiphile and DPPC at specific sites, with an average of four DPPC lipids bound to each amphiphile in the bilayer. An area per lipid calculation, done by a Voronoi tessellation, finds that the headgroup of the amphiphile is significantly smaller than that of DPPC, thus higher concentrations of amphiphile decrease the total lateral bilayer area. Diffusion coefficients of amphiphiles in the plane of the bilayer dramatically increase with decreasing amphiphile tail lengths. In addition, as the concentration of amphiphile increased, the diffusion coefficients of both the lipid and amphiphile increase, suggesting a strong influence of the amphiphiles on the bilayer systems. These results provide insight into the molecular interactions of the amphiphile molecules with the lipid bilayer, and provide a means to understand their potential impact in the biophysical properties of cellular membranes.