Solution Structure of Copper Ion-Induced Molecular Aggregates of Tyrosine Melanin

Abstract

Melanin, the ubiquitous biological pigment, provides photoprotection by efficient filtration of light and also by its antioxidant behavior. In solutions of synthetic melanin, both optical and antioxidant behavior are affected by the aggregation states of melanin. We have utilized small-angle x-ray and neutron scattering to determine the molecular dimensions of synthetic tyrosine melanin in its unaggregated state in D(2)O and H(2)O to study the structure of melanin aggregates formed in the presence of copper ions at various copper-to-melanin molar ratios. In the absence of copper ions, or at low copper ion concentrations, tyrosine melanin is present in solution as a sheet-like particle with a mean thickness of 12.5 A and a lateral extent of approximately 54 A. At a copper-to-melanin molar ratio of 0.6, melanin aggregates to form long, rod-like structures with a radius of 32 A. At a higher copper ion concentration, with a copper-to-melanin ratio of 1.0, these rod-like structures further aggregate, forming sheet-like structures with a mean thickness of 51 A. A change in the charge of the ionizable groups induced by the addition of copper ions is proposed to account for part of the aggregation. The data also support a model for the copper-induced aggregation of melanin driven by pi stacking assisted by peripheral Cu(2+) complexation. The relationship between our results and a previous hypothesis for reduced cellular damage from bound-to-melanin redox metal ions is also discussed.

Excitonic effects from geometric order and disorder explain broadband optical absorption in eumelanin

“…However, we cannot find similar aggregate structures in the snapshot of the monomeric model. In addition to the aggregate structures, the oligomeric models are also able to reproduce the mechanical properties of eumelanin including the mass density and Young's modulus in good agreement with the experimental measurements [36][37][38][39] (see Supplementary Discussion and Supplementary Fig. 5 for details).…”

Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis

“…The opposite was observed for D39-P8, D37-P9, and D43-P5, whose TREPR signals were mimicked by acidified synthetic melanin, where melanin is insoluble and aggregated. RPE cells under physiological conditions are not likely to be very acidic or very basic; nonetheless, several in vivo factors appear to influence or modulate melanin organization within cells, particularly metal ions (53)(54)(55)(56), RPE age (8,14,16), and proteins (9,34). In synthetic systems, pH is a main factor controlling the organization of melanin and determining the type of EPR-observable photochemistry that occurs (52).…”

The physical and chemical properties of eumelanin

“…From 1994 until the present, several theoretical and experimental studies have been published in support of the oligomeric secondary structure. Notably, Gallas et al (1999) used small angle X-ray scattering (SAXS) to suggest an oligomer size and stacking dimension, and Clancy and Simon (2001) used atomic force microscopy to investigate the ultrastructure of sepia eumelanin. More recently, Lorite et al (2006) have also published atomic force microscopy studies of synthetic eumelanin films prepared in both aqueous and organic solvents.…”