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Biomaterials

Biomaterials - Poster Session D

Poster D1 - Spectroscopic Analysis of Melanin Variants for Insights into Melanomagenesis

Friday, October 25, 2024
3:30 PM - 4:30 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Upwards of 1 million Americans currently live with melanoma, the most lethal form of skin cancer. This number is expected to rise, with nearly 100,000 new diagnoses projected by the end of 2024. Melanoma arises from the abnormal growth of melanocytes, which synthesize two types of melanin: eumelanin, which has antioxidant and photoprotective properties, and pheomelanin, which is carcinogenic and phototoxic due to its ability to generate reactive oxygen species. Though these pigments play a role in melanoma development, their structures have not yet been consistently identified. Melanin synthesis begins with the catalytic oxidation of 3,4-dihydroxyphenylalanine (L-DOPA) to dopaquinone by the enzyme tyrosinase. In the presence of cysteine, dopaquinone forms cysteinyldopa, leading to intermediates of pheomelanin. This project aims to modulate melanin synthesis pathways and generate consistent characterization data for pheomelanin and eumelanin.

Materials and

Methods:  Melanins can be synthesized in the lab using the chemical reagents found in the melanogenesis pathway. Using murine and human cell lines, experimental results were compared with cell-produced melanins to validate proposed structures. Fourier Transform Infrared Spectroscopy (FTIR) and Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFT) are used to analyze synthesized and cell-produced eumelanin and pheomelanin, allowing comparative analysis through peak identification of functional groups and structural properties. Additionally, Gaussian software on a High-Performance Computing cluster simulated vibrational spectra to identify the exact bonds contributing to specific peaks. Comparing simulated and experimental/cell-produced FTIR spectra provides insights into the structural properties and chemical behaviors of synthesized melanins, enhancing our understanding of the causes of melanoma and potential therapeutic strategies.

Results, Conclusions, and Discussions: This project has generated a comprehensive library of pheomelanin and eumelanin in varying ratios, characterized by FTIR spectral analysis. Cell lines hypothesized to produce pheomelanin were cultured, and melanosome extractions provided characterization data for cell–synthesized pheomelanin. Additionally, computational simulations based in literature have produced FTIR spectra for various subunits. Lab-synthesized melanins and their analogs further supported the diverse pigment compositions theorized to exist in human skin tissue. Future work will focus on conducting Principal Component Analysis (PCA) using an experimental FTIR library to quantify pheomelanin and eumelanin ratios in tissues. Optimization of simulation parameters will enhance the reliability of computational models. This study lays a foundational framework for advanced melanin research, potentially offering new insights into pigment-related disorders and their treatment.

Acknowledgements (Optional):  Case Comprehensive Cancer Center, Lerner Research Institute