A molecular dynamics study of the physical basis of stability of polypeptide multilayer nanofilms

Electrostatic layer-by-layer assembly (LBL) is a versatile method of fabricating ultrathin multilayer films, coatings, and microcapsules from materials in solution, notably, oppositely charged polyelectrolytes in water. Polypeptides, a special type of polyelectrolyte, have recently shown promise for a range of applications in biotechnology and medicine, for example, artificial cells, drug delivery systems, cell/tissue scaffolds, artificial viruses, and implantable device coatings. Poly(L-lysine) (PLL) and poly(L-glutamic acid) (PLGA) at neutral pH are model oppositely charged polypeptides. Experimental studies have shown that PLL/PLGA multilayer films contain a substantial amount of beta-sheets. Here, we present findings of a molecular dynamics (MD) study of the physical basis of interaction between PLL and PLGA in multilayer film models. Simulations have been carried out to study structural and dynamical properties of PLL/PLGA aggregates in beta-sheet conformation. The results suggest that hydrophobic interactions, in addition to electrostatics interactions, play a significant role in PLL/PLGA multilayers. The preferred orientation of peptides in the beta-sheet structures is antiparallel within sheets and parallel between sheets. Intersheet hydrogen-bond formation is more likely the result of peptide association than the cause. The approach provides a general means to understand better how various types of noncovalent interactions contribute to the structure and stability of polypeptide multilayer films.