Postnatal mechanical loading drives adaptation of tissues primarily through modulation of the non-collagenous matrix.

Danae E Zamboulis,Hazel Rc Screen,Yalda Ashraf Kharaz,Chavaunne T Thorpe,Peter D Clegg,Helen L Birch

doi:10.7554/elife.58075

Abstract

Mature connective tissues demonstrate highly specialised properties, remarkably adapted to meet their functional requirements. Tissue adaptation to environmental cues can occur throughout life and poor adaptation commonly results in injury. However, the temporal nature and drivers of functional adaptation remain undefined. Here, we explore functional adaptation and specialisation of mechanically loaded tissues using tendon; a simple aligned biological composite, in which the collagen (fascicle) and surrounding predominantly non-collagenous matrix (interfascicular matrix) can be interrogated independently. Using an equine model of late development, we report the first phase-specific analysis of biomechanical, structural, and compositional changes seen in functional adaptation, demonstrating adaptation occurs postnatally, following mechanical loading, and is almost exclusively localised to the non-collagenous interfascicular matrix. These novel data redefine adaptation in connective tissue, highlighting the fundamental importance of non-collagenous matrix and suggesting that regenerative medicine strategies should change focus from the fibrous to the non-collagenous matrix of tissue.

Highlights

Functional adaptation of load-bearing tissues such as tendon is crucial to ensure the tissue is specialised appropriately to meet functional needs
We identify the emergence of an extended region of low stiffness at the start of the loading curve specific to the superficial digital flexor tendon (SDFT) interfascicular matrix (IFM) pull to failure curve (Figure 2b)
The energy-storing SDFT, which functions by stretching and recoiling with each stride to store and return energy, undergoes peaks strains recorded at 16.6% in vivo and has been found to be significantly more extensible than the common digital extensor tendon (CDET)

Summary

Introduction

Functional adaptation of load-bearing tissues such as tendon is crucial to ensure the tissue is specialised appropriately to meet functional needs. As the principal structural component of connective tissues, collagen expression at the gene and protein level has been the focus of the majority of studies in relation to loading, with some studies reporting increases in collagen synthesis and others noting collagen degradation in response to loading, depending on the tissue function or tissue structure in different species (Choi et al, 2018; Magnusson and Kjaer, 2019) In tendons, this collagen structural framework is the fascicles and it is surrounded by the primarily non-collagenous and glycoprotein-rich components of the ECM, termed the interfascicular matrix (IFM) (Figure 1—figure supplement 1b; Armiento et al, 2018; Thorpe and Screen, 2016). We hypothesise that early in development during gestation, the fascicle and IFM of functionally distinct tendons have identical compositional profiles and mechanical properties, with tissue specialisation occurring as an adaptive response to the mechanical stimulus of load-bearing, predominantly in the IFM of the elastic energy-storing tendon

Results

Discussion

Materials and methods

Funding Funder Horserace Betting Levy Board