Visualizing collagen proteolysis by peptide hybridization: From 3D cell culture to in vivo imaging

Biomaterials
Lucas L BenninkS Michael Yu

Abstract

Degradation of the extracellular matrix (ECM) is one of the fundamental factors contributing to a variety of life-threatening or disabling pathological conditions. However, a thorough understanding of the degradation mechanism and development of new ECM-targeting diagnostics are severely hindered by a lack of technologies for direct interrogation of the ECM structures at the molecular level. Previously we demonstrated that the collagen hybridizing peptide [CHP, sequence: (GPO)9, O: hydroxyproline] can specifically recognize the degraded and unfolded collagen chains through triple helix formation. Here we show that fluorescently labeled CHP robustly visualizes the pericellular matrix turnover caused by proteolytic migration of cancer cells within 3D collagen culture, without the use of synthetic fluorogenic matrices or genetically modified cells. To facilitate in vivo imaging, we modified the CHP sequence by replacing each proline with a (2S,4S)-4-fluoroproline (f) residue which interferes with the peptide's inherent propensity to self-assemble into homo-triple helices. We show that the new CHP, (GfO)9, tagged with a near-infrared fluorophore, enables in vivo imaging and semi-quantitative assessment of osteolytic bone lesions in...Continue Reading

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Citations

Nov 14, 2019·Organic & Biomolecular Chemistry·Jesús M DonesRonald T Raines
Feb 19, 2020·PLoS Biology·Robin A WelshScheherazade Sadegh-Nasseri
Sep 16, 2019·Journal of Translational Medicine·Shuaishuai XuLiang Liu
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Feb 13, 2021·Journal of Personalized Medicine·Nithya Subrahmanyam, Hamidreza Ghandehari
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May 16, 2020·ACS Infectious Diseases·Aubrey J EllisonRonald T Raines
Oct 12, 2021·ACS Applied Materials & Interfaces·Venkanagouda S GoudarFan-Gang Tseng
Oct 27, 2021·Expert Opinion on Drug Delivery·Lucas C DunsheeKristi L Kiick
Nov 6, 2021·ACS Nano·Lei LiuYang Li
Oct 30, 2021·Journal of Thrombosis and Haemostasis : JTH·Blain JonesGunjan Agarwal

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