Defining Nascent Bone by the Molecular Nanomechanics of Mineralized Collagen Fibrils

Abstract

Here we focus on recent advances in understanding the deformation and fracture behavior of collagen, Nature's most abundant protein material and the basis for many biological composites including bone, dentin or cornea. We show that it is due to the basis of the collagen structure that leads to its high strength and ability to sustain large deformation, as relevant to its physiological role in tissues such as bone and muscle. Experiment has shown that collagen isolated from different sources of tissues universally displays a design that consists of tropocollagen molecules with lengths of approximately 300 nanometers. Using a combination of theoretical analyses and multi-scale modeling, we have discovered that the characteristic structure and characteristic dimensions of the collagen nanostructure is the key to the ability to take advantage of the nanoscale properties of individual tropocollagen molecules at larger scales, leading to a tough material at the micro- and mesoscale. This is achieved by arranging tropocollagen molecules into a staggered assembly at a specific optimal molecular length scale. During bone formation, nanoscale mineral particles precipitate at highly specific locations in the collagen structure. These mineralized collagen fibrils are highly conserved, nanostructural primary building blocks of bone. By direct molecular simulation of the bone's nanostructure, we show that it is due to the characteristic nanostructure of mineralized collagen fibrils that leads to its high strength and ability to sustain large deformation, as relevant to its physiological role, creating a strong and tough material. We present a thorough analysis of the molecular mechanisms of protein and mineral phases in deformation, and report discovery of a new fibrillar toughening mechanism that has major implications on the fracture mechanics of bone. Our studies of collagen and bone illustrate how hierarchical multi-scale modeling linking quantum chemistry with continuum fracture mechanics approaches can be used to develop predictive models of hierarchical protein materials. We conclude with a discussion of the significance of hierarchical multi-scale structures for the material properties and illustrate how these structures enable one to overcome some of the limitations of conventional materials design, combining disparate material properties such as strength and robustness.