Aggregation of Lipid A Variants: a Hybrid Particle-Field Model

Lipid A is one of three components of bacterial lipopolysaccharides (constituting the outer membrane of Gram-negative bacteria) and is recognized to have an important biological role in inflammatory response of the immune system. Its biological activity is modulated by the number of acyl-chains and from the electrostatic interactions with the different counter-ions. In this paper we report a coarse-grained model of poly-acyl Lipid A based on the hybrid particle field molecular dynamics approach (hPF-MD). In particular, we investigate the stability of Lipid A bilayer with two different acyl-chains, hexa- and tetra-. We find a good agreement of the particle distribution along the cross-section of bilayer by comparing the density profiles calculated from hPF-MD simulations with respect to reference all-atom. Moreover, we validate the model simulating the self-assembly of lamellar phase from an initial random distribution of Lipid A/N²⁺molecules in water. Finally, we test the stability of a vesicle composed of hexa-acylated Lipid A in water. The proposed model is able to maintain stable bilayer aggregates and spherical vesicle, and to correctly reproduce the phase behavior of Lipid A/Ca²⁺/Water mixture.