Metabolomic Profiling of Squid Chromatophores Reveals Differential Biochemical Fingerprints across Red, Yellow, and Brown Colors.

Cephalopods possess the ability to camouflage using specialized dermal organs, including chromatophores that modulate pigment-based color, iridophores that produce structural iridescence, and leucophores that scatter light to create diffuse white. Among these organs, chromatophores─present as yellow, red, and brown variants─contribute to rapid color changes during camouflage, as their multicellular architecture expands under neuromuscular control. While the general structure and function of chromatophores have been characterized, the specific biochemical features that drive their distinct pigmentation remain poorly understood. To address this gap, we performed untargeted LC-MS/MS metabolomics across manually isolated yellow, red, and brown chromatophores. We detected over 4,000 compounds with extensive overlap across all three chromatophore types. However, differential abundance patterns through directed pairwise comparisons revealed variation in metabolic activity among the colors, where yellow chromatophores exhibited enrichment in oxidative pathways, brown chromatophores showed enrichment in pigment-related metabolites, and red chromatophores displayed an intermediary state. While future targeted biochemical studies are required to connect these differences to their functional contributions in camouflage, our findings introduce a framework suggesting that chromatophore color identity stems from subtle differences across a metabolic continuum, rather than from discrete, isolated biochemical states. These differences may reflect a level of developmental programming of color unique to cephalopods.