State diagrams of type I collagen for the rational design of biomimetic materials

Ideally, designing tissue engineering grafts and 3D cell culture materials should rely on mimicking the architecture and composition of the extracellular matrix, which is predominantly comprised of type I collagen. However, while collagen molecules are assembled into fibrils by cells in vivo, well-organized fibrils rarely form spontaneously in vitro. Indeed, the physico-chemical conditions for fibrillogenesis are still poorly understood and their influence on the formation and properties of fibrillar biomimetic materials remains elusive. Here, we establish state diagrams for type I collagen over an unprecedented range of concentration and temperature, showing the collagen denaturation limits, the emergence of fibrils in acidic conditions, and a new regime of collagen molecule/fibril coexistence. We also show how the state diagrams can be used to understand the formation of biomimetic materials by classical methods, as illustrated here by collagen freeze-casting. Therefore, these state diagrams will help to optimize the production of collagen-based biomimetic materials.