Title : Site-Specific L-DOPA Incorporation in collagen-mimicking peptides: A novel biomaterials strategy
Abstract:
Collagen, a pivotal structural protein in the extracellular matrix (ECM), plays a critical role in providing mechanical stability and supporting cell functions, making it essential for tissue engineering (TE) applications. Our work leverages synthetic biology to engineer collagen-mimicking polypeptides (CMPs) expressed in E. coli, offering a scalable, cost-effective, reproducible, and genetically adaptable platform for producing biomaterials. By integrating non-canonical amino acids (ncAAs), such as L-3,4-dihydroxyphenylalanine (L-DOPA), at specific sites using the genetic code expansion method, we create “smart” CMPs with enhanced functionalities.
L-DOPA’s catechol side chain significantly improves molecular stability and self-assembly, forming triple-helical structures and promoting fibrillation under physiological conditions. Moreover, these engineered CMPs demonstrate superior biocompatibility, facilitating cell adhesion, spreading, and enhanced metabolic activity in 2-D hydrogels and 3-D scaffolds. The incorporation of L-DOPA allows precise modulation of CMP properties, enabling the creation of customizable biomaterials that adapt to various tissue engineering demands.
This innovative approach integrates TE and synthetic biology to produce biomaterials with tunable chemical and mechanical properties. The resulting smart CMPs respond effectively to cellular interactions, offering a sustainable, pathogen-free alternative to animal-derived collagen. By enabling cost-efficient and reproducible production, this system provides a versatile platform for advancing regenerative medicine, particularly in applications requiring adaptive biomaterials.
