Variation in type I collagen fibril nanomorphology: the significance and origin

Abstract

Although the axial D-periodic spacing is a well-recognized nanomorphological feature of type I collagen fibrils, the existence of a distribution of values has been largely overlooked since its discovery seven decades ago. Studies based on single fibril measurements occasionally noted variation in D-spacing values, but accredited it with no biological significance. Recent quantitative characterizations supported that a 10-nm collagen D-spacing distribution is intrinsic to collagen fibrils in various tissues as well as in vitro self-assembly of reconstituted collagen. In addition, the distribution is altered in Osteogenesis Imperfecta and long-term estrogen deprivation. Bone collagen is organized into lamellar sheets of bundles at the micro-scale, and D-spacings within a bundle of a lamella are mostly identical, whereas variations among different bundles contribute to the full-scale distribution. This seems to be a very general phenomenon for the protein as the same type of D-spacing/bundle organization is observed for dermal and tendon collagen. More research investigation of collagen nanomorphology in connection to bone biology is required to fully understand these new observations. Here we review the data demonstrating the existence of a D-spacing distribution, the impact of disease on the distribution and possible explanations for the origin of D-spacing variations based on various collagen fibrillogenesis models.

Self-Assembly Study of Type I Collagen Extracted from Male Wistar Hannover Rat Tail Tendons

“…It could be considered that this variation in the periodic spacing is intrinsic to the collagen type I self-assembly process, because of local changes in the mechanical stresses. Those changes are due to the variations in the intra-brillary interactions, including hydrophobic and electrostatic interactions, hydrogen bonds and crosslinks in hydroxylysine and hydroxyprolines [34]. Each bril diameter is between 450 and 550 nm, which coincides with the reported value for the tendons brils that are up to 1 cm long and 500 nm in diameter [35].…”

Alteration of Type I collagen microstructure induced by estrogen depletion can be prevented with drug treatment

“…6,7 Recent AFM studies indicated changes in the nanomorphology of the Type I collagen fibrils in ovariectomized (OVX) sheep [8][9][10] and rats. 11 In order to explore the effect of estrogen depletion and compare efficacy of CatKI and alendronate (ALN) drug treatments, the rabbit OVX model was developed by Merck Inc., as human CatKI's exhibit similar potency for the rabbit enzyme and the adult rabbit skeleton undergoes substantial cortical Haversian remodeling (unlike the rodent).…”

Synthesis and secretome release by human bone marrow mesenchymal stem cell spheroids within three‐dimensional collagen hydrogels: Integrating experiments and modelling

“…Collagen from different tissues undergo a series of unique post‐translational modifications that will govern the spatial organization, diameter, cross‐linking, and D‐spacing of the collagen fibrils (Fang & Holl, ). In addition, the processing conditions, such as temperature, pH, ionic strength, enzyme treatment, and the initial raw material, are known to influence collagen functional properties such as gelation rate, viscosity, and water retention capacity (Schmidt et al, ).…”

“…Thus, collagen cultures and specifically human collagen led to reduced expression of chemokines and pro-inflammatory cytokines but caused concomitant higher expression of immunomodulatory factor; such tuned MSC profile could be beneficial when administered to inflamed myocardium. Collagen from different tissues undergo a series of unique posttranslational modifications that will govern the spatial organization, diameter, cross-linking, and D-spacing of the collagen fibrils (Fang & Holl, 2013). In addition, the processing conditions, such as temperature, pH, ionic strength, enzyme treatment, and the initial raw material, are known to influence collagen functional properties such as gelation rate, viscosity, and water retention capacity (Schmidt et al, 2016).…”