title: Methacrylation induces rapid, temperature-dependent, reversible self-assembly of type-I collagen.
abstract: Type-I collagen self-assembles into a fibrillar gel at physiological temperature and pH to provide a cell-adhesive, supportive, structural network. As such, it is an attractive, popular scaffold for in vitro evaluations of cellular behavior and for tissue engineering applications. In this study, type-I collagen is modified to introduce methacrylate groups on the free amines of the lysine residues to create collagen methacrylamide (CMA). CMA retains the properties of collagen such as self-assembly, biodegradability, and natural bioactivity but is also photoactive and can be rapidly cross-linked or functionalized with acrylated molecules when irradiated with ultraviolet light in the presence of a photoinitiator. CMA also demonstrates unique temperature-dependent behavior. For natural type-I collagen, the overall structure of the fiber network remains largely static over time scales of a few hours upon heating and cooling at temperatures below its denaturation point. CMA, however, is rapidly thermoreversible and will oscillate between a liquid macromer suspension and a semisolid fibrillar hydrogel when the temperature is modulated between 10 and 37 °C. Using a series of mechanical, scattering, and spectroscopic methods, we demonstrate that structural reversibility is manifest across multiple scales from the protein topology of the triple helix up through the rheological properties of the CMA hydrogel. Electron microscopy imaging of CMA after various stages of heating and cooling shows that the canonical collagen-like D-periodic banding ultrastructure of the fibers is preserved. A rapidly thermoreversible collagen-based hydrogel is expected to have wide utility in tissue engineering and drug delivery applications as a biofunctional, biocompatible material. Thermal reversibility also makes CMA a powerful model for studying the complex process of hierarchical collagen self-assembly.
authors.affiliation: Department of Biomedical Engineering and ‡Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854, United States.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Drzewiecki
authors.forename: Avanish S
authors.initials: AS
authors.lastname: Parmar
authors.forename: Ian D
authors.initials: ID
authors.lastname: Gaudet
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Branch
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Pike
authors.forename: Vikas
authors.initials: V
authors.lastname: Nanda
authors.forename: David I
authors.initials: DI
authors.lastname: Shreiber
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis* / Q000737:chemistry; D024042:Collagen Type I / Q000138:chemical synthesis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000737:chemistry*; D010316:Particle Size; D013499:Surface Properties; D013696:Temperature
chemical_list: D000178:Acrylamides; D024042:Collagen Type I; D008689:Methacrylates; C045985:methacrylamide