Corneal collagen fibril structure in three dimensions: Structural insightsinto fibril assembly, mechanical properties, and tissue organization

The ability of the cornea to transmit light while being mechanically resili ent is directly attributable to the formation of an extracellular matrix co ntaining orthogonal sheets of collagen fibrils. The detailed structure of t he fibrils and how this structure underpins the mechanical properties and o rganization of the cornea is understood poorly. In this study, we used auto mated electron tomography to study the three-dimensional organization of mo lecules in corneal collagen fibrils. The reconstructions show that the coll agen molecules in the 36-nm diameter collagen fibrils are organized into mi crofibrils ( approximate to4-nm diameter) that are tilted by approximate to 15 degrees to the fibril long axis in a right-handed helix. An unexpected finding was that the microfibrils exhibit a constant-tilt angle independent of radial position within the fibril. This feature suggests that microfibr ils in concentric layers are not always parallel to each other and cannot r etain the same neighbors between layers. Analysis of the lateral structure shows that the microfibrils exhibit regions of order and disorder within th e 67-nm axial repeat of collagen fibrils. Furthermore, the microfibrils are ordered at three specific regions of the axial repeat of collagen fibrils that correspond to the N- and C-telopeptides and the d-band of the gap zone . The reconstructions also show macromolecules binding to the fibril surfac e at sites that correspond precisely to where the microfibrils are most ord erly.