Figure 1. Targeting denatured collagen using the concept of collagen hybridization.

(a) TEM images showing characteristic collagen fibril structures of normal human large airways and mice abdominal aorta compared to disorganized and truncated collagen fibrils from the asthmatic airways and abdominal aorta aneurysm. Adapted with permission from ref 153 (Copyright 2019 American Thoracic Society) and 154 (Copyright 2020 Elsevier Ltd.). (b) The triple-helix, the hallmark structure of the collagen molecule, may be denatured due to protease degradation (e.g., by MMPs) or mechanical disruption to the collagen fibrils. (c) The Collagen Hybridizing Peptide (CHP), often conjugated with a functional moiety (X, e.g., a fluorophore) can specifically target a denatured collagen molecule through the formation of a hybrid triple-helix. (d) The fluorescently-labeled CHP, but not the anti-Col IV antibody, detects collagen degradation histologically within the glomeruli of nephritic rats. (c) and (d) adapted with permission from ref 41. Copyright 2017 American Chemical Society. (e) The fluorescence from the CHP staining increased with incremental strain levels within the stretched center of the rat tail tendon fascicles, reflecting molecular denaturation of collagen from mechanical damage. Adapted with permission under a Creative Commons Attribution 4.0 License from ref 6. Copyright 2017 Springer Nature. (f) In vivo binding: CHP targets denatured collagen within normal mice intervertebral discs sandwiched between the vertebral bodies marked by OsteoSense and MMPSense. ^SCHP: sequence-scrambled control peptide. (g) Light sheet microscopy 3D fluorescence imaging showing denatured collagen marked by in-vivo-administered CHP in the intervertebral disc (ivd), facet joints (fj), and the attachment point (ap) of the supraspinous ligament on a spinous process of a rat lumbar spine. (f) and (g) adapted with permission from ref 49. Copyright 2021 American Chemical Society.