Imaging and targeting LOX-mediated tissue remodeling with a reactive collagen peptide

Aronoff, Matthew R.; Hiebert, Paul; Hentzen, Nina B.; Werner, Sabine; Wennemers, Helma

Abstract

Collagens are fibrous proteins that are integral to the strength and stability of connective tissues. During collagen maturation, lysyl oxidases (LOX) initiate the cross-linking of fibers, but abnormal LOX activity is associated with impaired tissue function as seen in fibrotic and malignant diseases. Visualizing and targeting this dynamic process in healthy and diseased tissue is important, but so far not feasible. Here we present a probe for the simultaneous monitoring and targeting of LOX-mediated collagen cross-linking that combines a LOX-activity sensor with a collagen peptide to chemoselectively target endogenous aldehydes generated by LOX. This synergistic probe becomes covalently anchored and lights up in vivo and in situ in response to LOX at the sites where cross-linking occurs, as demonstrated by staining of normal skin and cancer sections. We anticipate that our reactive collagen-based sensor will improve understanding of collagen remodeling and provide opportunities for the diagnosis of fibrotic and malignant diseases. [Figure not available: see fulltext.].

Citation

Aronoff, M. R., Hiebert, P., Hentzen, N. B., Werner, S., & Wennemers, H. (2021). Imaging and targeting LOX-mediated tissue remodeling with a reactive collagen peptide. Nature Chemical Biology, 17(8), 865-871. https://doi.org/10.1038/s41589-021-00830-6

• Journal Article Type: Article
• Acceptance Date: Jun 9, 2021
• Online Publication Date: Jul 12, 2021
• Publication Date: Aug 1, 2021
• Deposit Date: Feb 20, 2024
• Journal: Nature Chemical Biology
• Print ISSN: 1552-4450
• Electronic ISSN: 1552-4469
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 8
• Pages: 865-871
• DOI: https://doi.org/10.1038/s41589-021-00830-6
• Public URL: https://hull-repository.worktribe.com/output/4554015