Collagen hybridizing peptide to target in vivo misfolded collagen in OI zebrafish.
Collagen hybridizing peptide (CHP) just scored a win in zebrafish research. Scientists put a fluorescent tag on CHP and used it to hunt down misfolded collagen in a model of osteogenesis imperfecta (OI). This isn’t just another stain—it’s a selective tool that goes after the pathological collagen itself, right in live animals.
Sci Rep
by Tonelli F, Aresi C, Masiero C et al.
“Collagen hybridizing peptide to target in vivo misfolded collagen in OI zebrafish. Tonelli F(1), Aresi C(1), Masiero C(1), Gioia R(2), Morrison T(3), Rossi A(1), Yu SM(3), Forlino A(4)(5). Author information: (1)Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Via Taramelli 3/b, Pavia, 27100, Italy. (2)Biomedical Imaging Laboratory, Centro Grandi Strumenti, University of Pavia, Pavia, Italy. (3)Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA. (4)Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Via Taramelli 3/b, Pavia, 27100, Italy. antonella.forlino@unipv.it. (5)Research Platform, IRCCS San Matteo, Pavia, Italy. antonella.forlino@unipv.it. Osteogenesis imperfecta (OI) is a heritable connective tissue disorder characterized by defects in collagen I, leading to increased bone fragility and turnover. The zebrafish Chihuahua (Chi/+), carrying a p.(Gly736Asp) substitution in the α1(I) chain, recapitulates key features of human OI, including the presence of misfolded collagen I in extracellular matrix. In this study, we evaluated the specificity of a fluorescently labeled collagen hybridizing peptide (Cy5-CHP) for detecting in vivo misfolded collagen I in adult zebrafish. The CHP or the scrambled control peptides were injected intraperitoneally into WT and Chi/+ zebrafish, and average radiant efficiency was quantified at 24 and 72 h post-injection (hpi) in the vertebral column, cranium and heart, representing collagen I-rich organs, as well as the brain, a collagen I-poor tissue. Our results revealed Cy5-CHP specific binding to collagen I-rich tissues in Chi/+ zebrafish at 24 hpi, with minimal signal in the brain, whereas low signal was detectable across all tissues in WT. Cy5-CHP fluorescence was reduced by 72 hpi in all samples, consistent with the low binding affinity of the peptide. Histological analyses confirmed the co-localization of Cy5-CHP with collagen fibers in the endplates of Chi/+ vertebrae at 24 hpi. These findings provide the first in vivo evidence in zebrafish that Cy5-CHP selectively binds misfolded collagen, showing preferential accumulation in collagen I-rich tissues in OI. Overall, the results support the use of Cy5-CHP as a sensitive tool for detecting pathologic collagen and as a potential platform for tissue-targeted drug delivery in OI and other collagen-related disorders. © 2026. The Author(s). Conflict of interest statement: Declarations. Competing interests: The authors declare no competing interests.”
The setup: Researchers injected Cy5-labeled CHP into both wild-type and OI-model zebrafish (the “Chi/+” line). They checked for the fluorescent signal in areas rich in collagen I—vertebral column, cranium, heart—and compared it to the brain, which doesn’t have much collagen I. At 24 hours, CHP lit up the OI zebrafish’s bones and heart, but not the brain. Wild-type fish barely registered. By 72 hours, the signal faded, lining up with CHP’s known low binding affinity.
Key takeaway: Cy5-CHP is highly specific for misfolded collagen in vivo. Histology confirmed it—CHP actually co-localized with misfolded collagen fibers in the OI fish. This is the first time anyone has shown in a living organism that CHP can target and bind to misfolded collagen, not just in a dish.
Why it matters:
CHP could become a go-to tool for detecting pathological collagen in OI and similar diseases.
There’s potential for targeted drug delivery—CHP could guide compounds straight to problematic tissue.
This opens new directions for in vivo monitoring of collagen disorders, not just in zebrafish.
The research community now has a proof-of-concept for targeted peptide detection of misfolded matrix proteins. For more on the science and applications, check out the peptide research index. This is the kind of work that pushes the field forward—one targeted peptide at a time.
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