Development of the FP121 series: Hybrid proteins mimicking marine adhesive proteins with cell adhesion and proliferation activity

Marine adhesive proteins exhibit unique underwater adhesion properties and biological functionalities. While previous studies have emphasized DOPA-mediated adhesion, the physiological roles of epidermal growth factor (EGF) domains within these proteins remain largely unexplored. In this study, we de...

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Bibliographic Details
Main Authors: Yutaro Kawakami, Nobue Shishioh, Atsushi Ogura
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Materials & Design
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Online Access:http://www.sciencedirect.com/science/article/pii/S0264127525005738
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Summary:Marine adhesive proteins exhibit unique underwater adhesion properties and biological functionalities. While previous studies have emphasized DOPA-mediated adhesion, the physiological roles of epidermal growth factor (EGF) domains within these proteins remain largely unexplored. In this study, we developed a new series of recombinant hybrid proteins, FP121, combining the adhesive FP1 domain with the EGF-containing FP2 domain to evaluate their manufacturability and bioactivity. Among the constructs, FP121-6 demonstrated the highest solubility and expression yield, enabling efficient purification without denaturants. Functional assays revealed that FP121 proteins promote robust cell adhesion comparable to commercial CELL-TAK, regardless of DOPA modification. Moreover, FP121-6 significantly stimulated HeLa cell proliferation under serum-free conditions, suggesting a previously unrecognized growth-promoting function of FP2. Scratch assays confirmed enhanced cell migration by FP121 proteins, particularly when lacking His-tags. Structural analysis and sequence alignment with known EGF-like domains suggest potential heparin-binding functionality in FP2. These findings reveal that the FP121 series combines both adhesive and proliferative properties, offering a promising platform for tissue engineering and regenerative medicine. The high solubility and scalable production of FP121 proteins further support their applicability in biomedical devices and cell culture systems.
ISSN:0264-1275