Building Thermosensitive Single-Component Protein Hydrogels from De Novo Designed Homodimers

Abstract

Leveraging recent advances in protein design, we explored de novo designed proteins as building blocks for hydrogels. Specifically, we investigated two homodimers, a highly stable β-barrel dimer and a helical dimer. By incorporating elastin-like polypeptide (ELP) segments, we developed a novel gelation mechanism that enables recombinant proteins to self-assemble into hydrogels in a temperature-dependent manner, exhibiting a sol-gel transition near body temperature. Our results demonstrate that the secondary structure of the protein building blocks plays a crucial role in determining the mechanical properties and microstructure of the resulting hydrogels. The β-barrel homodimer-based hydrogels exhibited superior mechanical strength at lower temperatures due to their stable hydrogen bonding networks. Additionally, these hydrogels displayed excellent drug encapsulation capabilities and fatigue resistance, underscoring their potential for biomedical applications. This work advances our understanding of protein architecture in guiding hydrogel behavior and offers a versatile platform for tailored biomedical materials.