Abstract
The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tissue and organ level, the main aim of this study was to investigate how the structure and mechanics are altered in OIM collagen fibrils. Comparing results from atomic force microscopy imaging and cantilever-based nanoindentation on collagen fibrils from OIM and wild-type (WT) animals, we found a 33% lower indentation modulus in OIM when air-dried (bound water present) and an almost fivefold higher indentation modulus in OIM collagen fibrils when fully hydrated (bound and unbound water present) in phosphate-buffered saline solution (PBS) compared with WT collagen fibrils. These mechanical changes were accompanied by an impaired swelling upon hydration within PBS. Our experimental and atomistic simulation results show how the structure and mechanics are altered at the individual collagen fibril level as a result of collagen gene mutation in OIM. We envisage that the combination of experimental and modelling approaches could allow mechanical phenotyping at the collagen fibril level of virtually any alteration of collagen structure or chemistry.
Highlights
atomic force microscopy (AFM) experiments as well as atomistic simulations show that collagen fibrils are characterized by altered hydration, structural properties and, mechanical function as a consequence of deletion of COL1A2 gene
Owing to the higher bound water content in air-dried osteogenesis imperfecta (OIM) collagen fibrils compared with WT ones, the intermolecular separation is larger, which is responsible for the lower indentation modulus, as confirmed by our atomistic simulations
The situation is reversed upon full hydration, leading to a significantly higher indentation modulus of OIM collagen fibrils compared with WT ones
Summary
Collagen is a family of proteins that compose approximately 30% of the protein mass of the human body [1]. This makes collagen one of the most abundant proteins in humans as well as vertebrates and perhaps, the most important protein family providing structural and mechanical stability to almost every biological tissue in our bodies. The characteristic structure of collagen molecules has been proposed over 50 years ago on the basis of X-ray diffraction [2]. At the lowest length-scale level, three polypeptide alpha (a) chains are closely packed into a right-handed twisted helix (figure 1a; collagen structure from Protein Data Bank; PDB 1Cag [3]). The close packing into a triple helix is mediated by the high content
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