Nanomechanical sequencing of collagen: tropocollagen features heterogeneous elastic properties at the nanoscale.

Collagen is the most important structural protein in biology and is responsible for the strength and integrity of tissues such as bone, teeth, cartilage and tendon. Here we report a systematic computational sequencing of the effect of amino acid motif variations on the mechanical properties of single tropocollagen molecules, with a particular focus on elastic deformation at varying applied strains. By utilizing a bottom-up computational materiomics approach applied to four model sequence motifs found in human type I collagen, we show that variations in the amino acid motif severely influence the elastic behavior of tropocollagen molecules, leading to softening or stiffening behavior. We also show that interpeptide interactions via H-bonds vary strongly with the type of motif, which implies that it plays a distinct role in the molecule's stability. The most important implication of our results is that deformation in tropocollagen molecules is highly inhomogeneous, since softer regions deform more than stiffer regions, potentially leading to strain and stress concentrations within collagen fibrils. We confirm the hypothesis of inhomogeneous molecular deformation through direct simulation of stretching of a segment of tropocollagen from human type I collagen that features the physiological amino acid sequence. Our results show that the biomechanical properties of tropocollagen must be understood in the context of the specific amino acid sequence as well as the state of deformation, since the elastic properties depend strongly on the amount of deformation applied to a molecule.