Molecular and Mesoscale Mechanisms of Osteogenesis Imperfecta Disease

Collagen is a crucial structural protein material, formed through a hierarchical assembly of tropocollagen molecules, arranged in collagen fibrils that constitute the basis for larger-scale fibrils and fibers. Osteogenesis imperfecta is a genetic disorder in collagen characterized by mechanically weakened tendon, fragile bones, skeletal deformities and in severe cases prenatal death. Even though many studies have attempted to associate specific mutation types with phenotypic severity, the mechanisms by which a single point mutation influences the mechanical behavior of tissues at multiple length-scales remain unknown. In this study, we report a series of systematic molecular scale based bottom-up computational experiments focused on pure collagenous tissue, carried out using atomistic-level molecular dynamics (MD), adaptive Poison-Boltzmann solver (APBS) calculations, and a mesoscale molecular model of collagen fibrils.