Spatially differentiated byssus-related responses of the mussel foot to iron stimulation inform bioinspired adhesive fabrication.

Marine mussels fabricate durable underwater adhesives through coordinated precursor production, secretion, and metal-mediated assembly, yet the organization of these events within the foot remains poorly understood. In this study, anatomical, transcriptional, histochemical, and PBS-extractable protein analyses were integrated to characterize the foot of Mytilus coruscus under contrasting high- and low-concentration FeCl3 conditions (Fe1 and Fe2). The foot exhibited regional specialization. Plaque glands were concentrated distally, several Mfp transcripts were enriched in distal layers, PTMP transcript abundance was highest proximally, and preCOL-P showed its highest basal abundance in the middle region. Fe2 elicited a broad preCOL-P response across most regions and a localized increase in nitroblue tetrazolium-glycinate-positive area in the middle foot, whereas Fe1 was associated with distinct regional changes in collagen distribution and PBS-extractable band profiles. Foot tissues and collected secreted fractions also showed non-equivalent banding patterns, demonstrating that the secreted material did not simply mirror the tissue-extractable pool. Together, the divergence among transcriptional, histochemical, and protein-extractability patterns supports a working model in which early precursor-related processes are spatially separated yet functionally coordinated along the foot prior to final byssal assembly. These findings suggest testable design principles for bioinspired underwater adhesives based on spatial precursor management and controlled activation, while providing a framework for future studies to determine how early regional processing is translated into mature byssus composition and performance. STATEMENT OF SIGNIFICANCE: Marine mussel adhesion is well characterized at the level of mature byssal chemistry, but the spatial organization of precursor processing within the foot remains unclear. Using the non-model marine mussel Mytilus coruscus, this study integrates regional anatomy, targeted transcription, histochemistry, and PBS-extractable protein profiling to identify organ-scale spatial differentiation of early byssus-related processing. The middle foot emerges as a candidate zone for precursor conditioning and protein-state reorganization, while contrasting FeCl3 conditions reveal region-dependent responses shaped by physicochemical context and tissue organization. Beyond providing a spatial framework for byssal processing in a non-model biomaterials system, these findings suggest testable principles for precursor compartmentalization and controlled activation, and provide a basis for future validation in mature byssus.