Targeting collagen strands by photo-triggered triple-helix hybridization

Yang Li, Catherine A. Foss, Daniel D. Summerfield, Jefferson J. Doyle, Collin M. Torok, Harry C. Dietz, Martin G. Pomper, S. Michael Yu

Research output: Contribution to journalArticle

Abstract

Collagen remodeling is an integral part of tissue development, maintenance, and regeneration, but excessive remodeling is associated with various pathologic conditions. The ability to target collagens undergoing remodeling could lead to new diagnostics and therapeutics as well as applications in regenerative medicine; however, such collagens are often degraded and denatured, making them difficult to target with conventional approaches. Here, we present caged collagen mimetic peptides (CMPs) that can be photo-triggered to fold into triple helix and bind to collagens denatured by heat or by matrix metalloproteinase (MMP) digestion. Peptide-binding assays indicate that the binding is primarily driven by stereo-selective triple-helical hybridization between monomeric CMPs of high triple-helical propensity and denatured collagen strands. Photo-triggered hybridization allows specific staining of collagen chains in protein gels as well as photo-patterning of collagen and gelatin substrates. In vivo experiments demonstrate that systemically delivered CMPs can bind to collagens in bones, as well as prominently in articular cartilages and tumors characterized by high MMP activity. We further show that CMP-based probes can detect abnormal bone growth activity in a mouse model of Marfan syndrome. This is an entirely new way to target the microenvironment of abnormal tissues and could lead to new opportunities for management of numerous pathologic conditions associated with collagen remodeling and high MMP activity.

Original languageEnglish (US)
Pages (from-to)14767-14772
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number37
DOIs
StatePublished - Sep 11 2012

Keywords

  • Caged peptide
  • Cancer
  • Connective tissue
  • Degenerative disease
  • Diagnostic imaging

ASJC Scopus subject areas

  • General

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