De novo design of alpha-helical peptide amphiphiles repairing fragmented collagen type I via supramolecular co-assembly

Shanshan Su; Jie Yang; Guo Zhang; Zhiquan Yu; Yuxuan Chen; Alexander van Teijlingen; Dawen Yu; Tong Li; Yubin Ke; Hua Yang; Haoran Zhang; Jialong Chen; Jiaming Sun; Yuanhao Wu

arXiv · 2507.14577

De novo design of alpha-helical peptide amphiphiles repairing fragmented collagen type I via supramolecular co-assembly

Shanshan Su·Jie Yang·Guo Zhang·Zhiquan Yu·Yuxuan Chen·Alexander van Teijlingen·Dawen Yu·Tong Li·Yubin Ke·Hua Yang·Haoran Zhang·Jialong Chen·Jiaming Sun·Yuanhao Wu

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Abstract

The hierarchical triple-helix structure of collagen type I, Col I, is essential for extracellular matrix support and integrity. However, current reconstruction strategies face challenges such as chain mismatch, preventing proper fibril formation. Here, we report a supramolecular co-assembly strategy using a de novo-designed alpha-helical peptide amphiphile (APA) of just seven amino acids. The APA features a hydrophobic palmitic acid tail, which stabilizes the helical structure and promotes co-assembly upon interaction with complementary molecular structures. This minimal design enables selective recognition of fragmented collagen (FC), restoring triple-helix conformation and guiding fibre formation. We applied this mechanism to engineer FC-rich nanofat (NF) into a mechanically reinforced biomaterial. Integration of APA-NF with coaxial 3D printing enabled spatial control of structure and function. In a porcine model, this platform enhanced in situ vascularized adipose tissue regeneration. Our results demonstrate that hierarchical reconstruction of collagen via peptide-guided supramolecular assembly offers a promising strategy for soft tissue repair.

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Shanshan Su, Jie Yang, Guo Zhang, Zhiquan Yu, Yuxuan Chen, Alexander van Teijlingen, Dawen Yu, Tong Li, Yubin Ke, Hua Yang, Haoran Zhang, Jialong Chen, Jiaming Sun, Yuanhao Wu. 2025-07-19. De novo design of alpha-helical peptide amphiphiles repairing fragmented collagen type I via supramolecular co-assembly. https://arxiv.org/abs/2507.14577

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