Uniform spatial distribution of collagen fibril radii within tendon implies local activation of pC-collagen at individual fibrils

TL;DR

This study investigates how collagen fibrils grow uniformly within tendons, proposing that local activation of precursor molecules at individual fibrils explains the consistent fibril radii and the absence of new fibril formation after birth.

Contribution

It introduces a model suggesting local activation of collagen precursors at fibril surfaces explains uniform fibril radii and constrains precursor diffusion during tendon development.

Findings

Homogeneous fibril radii imply local precursor activation.

Diffusion bounds are marginally consistent with processed collagen.

Local C-proteinase activity likely facilitates fibril growth.

Abstract

Collagen fibril cross-sectional radii show no systematic variation between the interior and the periphery of fibril bundles, indicating an effectively constant rate of collagen incorporation into fibrils throughout the bundle. Such spatially homogeneous incorporation constrains the extracellular diffusion of collagen precursors from sources at the bundle boundary to sinks at the growing fibrils. With a coarse-grained diffusion equation we determine stringent bounds, using parameters extracted from published experimental measurements of tendon development. From the lack of new fibril formation after birth, we further require that the concentration of diffusing precursors stays below the critical concentration for fibril nucleation. We find that the combination of the diffusive bound, which requires larger concentrations to ensure homogeneous fibril radii, and lack of nucleation, which requires lower concentrations, is only marginally consistent with fully-processed collagen using conservative bounds. More realistic bounds may leave no consistent concentrations. Therefore, we propose that unprocessed pC-collagen diffuses from the bundle periphery followed by local C-proteinase activity and subsequent collagen incorporation at each fibril. We suggest that C-proteinase is localized within bundles, at fibril surfaces, during radial fibrillar growth. The much greater critical concentration of pC-collagen, as compared to fully-processed collagen, then provides broad consistency between homogeneous fibril radii and the lack of fibril nucleation during fibril growth.