The regulatory effects of proteoglycans on collagen fibrillogenesis and morphology investigated using biomimetic proteoglycans.
Collagen is one of the leading components in extracellular matrix (ECM), providing durability, structural integrity, and functionality for many tissues. Regulation of collagen fibrillogenesis and degradation is important for treating several diseases from orthopedic injuries to genetic deficiencies. In vivo, this process is generally regulated by proteoglycans (PGs), a family of molecules that contain both protein and glycosaminoglycan components. Recently, novel, biocompatible, semi-synthetic biomimetic proteoglycans (BPGs) were developed, which consist of an enzymatically resistant synthetic polymer core and natural chondroitin sulfate (CS) bristles. It was demonstrated that BPGs affect type I collagen fibrillogenesis in vitro, as reflected by their impact delaying the kinetic formation of gels similar to native PGs. To elucidate the interaction and the effect of BPGs on the quality of collagen fibrils, a histological technique, electron tomography, was adapted and utilized to image nano-scale structures in 2D and 3D within the tissue model. BPGs were found to aid in lateral growth and enhance fibril banding periodicity resulting in structures resembling those in native tissue. BPGs attached to collagen despite the lack of a protein core. This interaction was mediated by the CS bristle regions of the BPGs, implying that CS itself is sufficient for PG-type I tropocollagen interactions, in the absence of the protein core, with the overall nanoarchitecture of the molecule serving to affect ECM kinetics. Synthetic mimics are a tool to study non-proteinaceous PG interactions in collagen assembly and warrant exploration as a viable pathway to augmenting molecular repair in collagen type I-rich tissues.