Protein fibril-based delivery systems for bioactive substances: Structural design, functional regulation, and food...

Protein fibrils (PFs) are β-sheet-rich supramolecular assemblies with high aspect ratios, tunable surface chemistry, and multiscale assembly behavior, making them promising food-grade carriers for bioactive compounds. However, their delivery performance depends not simply on increasing fibril order or structural stability, but on balancing carrier robustness with molecular binding and release behavior. This review examines the regulatory mechanisms of PFs and the roles of key structural features in governing their physicochemical and biological activities, treating PFs as foundational templates rather than direct raw materials. Emphasis is placed on the controllable optimization of delivery performance through multidimensional structural design strategies. In particular, structural stability does not necessarily equate to better delivery performance; rather, a moderate balance must be maintained. By synergistically regulating solubility, structural stability, release behavior, and functional interactions, PF-based carriers can achieve systematic improvements in delivery performance. Such regulation allows PF-based carriers to address critical challenges in food systems, particularly poor dispersibility, limited stability, and low bioaccessibility of bioactive compounds. Their hierarchical architectures enable localized microenvironment modulation for improved delivery efficiency. Moreover, integrating conventional experimentation with deep learning offers new opportunities to predict and optimize fibril-matrix interactions, structural transitions, and performance enhancement. As multifunctional delivery platforms in food systems, PF-based carriers hold considerable promise for functional food design and nutritional fortification.