Self-Assembly of Allomelanin Dimers and the Impact of Poly(ethylene glycol) on the Assembly: A Molecular Dynamics Simulation Study.

Synthetic melanin nanoparticles that exhibit properties analogous to naturally found allomelanin can be formed by assembly of dimers/oligomers of the synthetic precursor of allomelanin, 1,8-dihydroxy naphthalene (DHN). To link the nanostructure within these assembled melanin nanoparticles to DHN dimer structure, we use explicit-solvent atomistic molecular dynamics (MD) simulations to study assembly of DHN dimers (2-2', 2-4', and 4-4' and their mixture) into nanoparticles in aqueous solutions. We analyze how the dimer structure and mixture composition impact the molecular interactions that drive assembly, as well as the assembled nanostructure, both internally and on the surface. We find that, prominently, hydrogen-bonding interactions drive the assembly of like-dimers, whereas unlike-dimer stacking interactions play a role in the assembly of dimer mixtures. The aggregate/nanoparticle assembled from 2-2' dimers assumes a spherical morphology as opposed to 4-4' dimers that adopt an anisotropic shape. The surface of the aggregate formed by 2-2' dimers is primarily hydrophobic, while the surface of aggregates formed by 2-4' dimers, 4-4' dimers, and their mixtures is amphiphilic. We also find that the addition of linear poly(ethylene glycol) (PEG) chains to the assembled particle does not alter the aggregate structure formed by a single dimer type. However, the PEG chains prefer to interact with 4-4' dimers more than with 2-2' and 2-4'. In aggregates formed by mixtures of dimers, PEG chains interact preferentially with 2-4' dimers than with 4-4' and 2-2' dimers.