Heterogeneity of proteome dynamics between connective tissue phases of adult tendon

Abstract

1Maintenance of connective tissue integrity is fundamental to sustain function, requiring 2 protein turnover to repair damaged tissue. However, connective tissue proteome dynamics 3 remain largely undefined, as do differences in turnover rates of individual proteins in the 4 collagen and glycoprotein phases of connective tissue extracellular matrix (ECM). Here, we 5 investigate proteome dynamics in the collagen and glycoprotein phases of connective tissues 6 by exploiting the spatially distinct fascicular (collagen-rich) and interfascicular (glycoprotein-7 rich) ECM phases of tendon. Using isotope labelling, mass spectrometry and bioinformatics, 8 we calculate turnover rates of individual proteins within rat Achilles tendon and its ECM 9 phases. Our results demonstrate complex proteome dynamics in tendon, with ~1000-fold 10 differences in protein turnover rates, and overall faster protein turnover within the 11 glycoprotein-rich interfascicular matrix compared to the collagen-rich fascicular matrix. 12These data provide insights into the complexity of proteome dynamics in tendon, likely 13 required to maintain tissue homeostasis. 14