Three years ago, Buehler used atomistic-based multi-scale modeling to describe in detail the hierarchical structure of collagen, the tissue comprising most structural material in mammalian bodies. His model incorporates a bottom-up description of collagen, accounting for the hierarchical assembly of molecules, each of which consists of three helical threads of amino acids. The molecules are arranged in packets called fibrils that collectively make up whole tissue.

In new research, Buehler and Sebastian Uzel, a graduate student at MIT, and Alfonso Gautieri, Alberto Redaelli and Simone Vesentini of Politecnico di Milano modeled type I collagen's behavior at the atomistic level all the way up to the scale of the fibrils that make up whole tissue.

The different forms of severity in brittle bone disease correlate with a particular genetic mutation; some amino acid substitutions for glycine create more severe forms of osteogenesis imperfecta.

Using atomistic modeling, the researchers demonstrate exactly how the substitution of eight different amino acids in place of glycine changes the electrochemical behavior of the collagen molecules and affects the mechanical properties of the collagen tissue. They learned that the mutations creating the most severe form of the disease also correlate with the greatest magnitude of adverse effects in creating more pronounced rifts in the tissue, which lead to the deterioration and failure of the tissue.

"The study of how the nature of the genetic makeup influences the mechanical behavior of materials is an important frontier in bioengineering," said Uzel. "It could potentially revolutionize the way we understand, model and treat medical disorders, and may also lead to the development of new biomaterials for applications in tissue engineering and regenerative medicine."

This work was funded by a National Science Foundation CAREER Award, the Army Research Office, the Progetto Rocca Fund and the MIT-Italy Program.

web.mit