Chiral interactions between tropocollagen molecules determine the collagen microfibril structure

Collagen is the most abundant structural protein in animals, forming hierarchically organised fibrils that provide mechanical support to tissues. Despite detailed structural studies, the physical principles that govern the formation of the characteristic axially-periodic collagen microfibril remain poorly understood. Here, we present a theoretical framework that links the amino acid sequence of tropocollagen to its supramolecular organisation. By combining statistical modeling of residue geometry with sequence-informed interaction potentials, we show that the chiral arrangement of outward-facing residues induces directional intermolecular interactions that drive molecular supercoiling. These interactions favour the formation of right-handed, pentameric microfibrils with a staggered axial periodicity of approximately 67 nm. Our simulations reveal that this structure emerges across a wide range of mammalian collagen sequences as a global energy minimum robust to biochemical noise. These findings provide a mechanistic explanation for collagen's supramolecular chirality and offer design principles for engineering synthetic collagen-mimetic materials.