Harnessing Peptide Self-Assembly for Advanced Biomimetic Cryopreservatives

Abstract

Peptide self-assembly represents a powerful approach for developing functional biomaterials that mimic natural systems. We explore the application of this supramolecular strategy in creating biomimetic cryoprotectants inspired by ice-binding proteins. Among them, antifreeze peptides (AFPs) control ice crystal formation through precisely arranged binding domains, but their practical use is limited by extraction challenges and instability issues. Our research focuses on the rational design of short peptide sequences that self-assemble into nanostructures with enhanced ice recrystallization inhibition properties. These supramolecular assemblies create collective arrangements of ice-binding moieties that significantly amplify their interaction with ice crystals. By controlling supramolecular organization, we achieve superior cryoprotective properties compared to individual molecular units. We've also developed organic-inorganic nanohybrids, enabling precise control over ice-water interface interactions through size and shape modulation. The optical properties of these nanohybrids allow direct visualization of ice recrystallization inhibition, providing mechanistic insights. Our studies reveal that the collective behavior of functional groups within these self- assembled structures is crucial for enhanced performance. By matching spatial arrangements to ice crystal lattices, we optimize thermodynamic control of ice formation. These peptide assemblies demonstrate excellent efficacy in cellular cryopreservation with significantly reduced cytotoxicity compared to conventional agents like dimethyl sulfoxide. This versatile approach allows for customizable designs tailored to specific applications in cell preservation, biobanking, and pharmaceutical storage. By bridging natural AFP functions and synthetic systems through controlled self-assembly, we offer promising solutions to long-standing challenges in cryopreservation technologies.