Glycation changes molecular organization and charge distribution in type I collagen fibrils.


Type
Article
Change log
Authors
Bansode, Sneha 
Bashtanova, Uliana 
Li, Rui 
Clark, Jonathan 
Müller, Karin H 
Abstract

Collagen fibrils are central to the molecular organization of the extracellular matrix (ECM) and to defining the cellular microenvironment. Glycation of collagen fibrils is known to impact on cell adhesion and migration in the context of cancer and in model studies, glycation of collagen molecules has been shown to affect the binding of other ECM components to collagen. Here we use TEM to show that ribose-5-phosphate (R5P) glycation of collagen fibrils - potentially important in the microenvironment of actively dividing cells, such as cancer cells - disrupts the longitudinal ordering of the molecules in collagen fibrils and, using KFM and FLiM, that R5P-glycated collagen fibrils have a more negative surface charge than unglycated fibrils. Altered molecular arrangement can be expected to impact on the accessibility of cell adhesion sites and altered fibril surface charge on the integrity of the extracellular matrix structure surrounding glycated collagen fibrils. Both effects are highly relevant for cell adhesion and migration within the tumour microenvironment.

Description
Keywords
Animals, Collagen Type I, Extracellular Matrix, Glycosylation, Humans, Ribosemonophosphates
Journal Title
Sci Rep
Conference Name
Journal ISSN
2045-2322
2045-2322
Volume Title
Publisher
Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/M01066X/1)
Royal Society (12737)
Simons Foundation (598399)
British Heart Foundation (None)
Medical Research Council (MR/J007692/1)
This project was substantially funded by the Medical Research Council (MRC), UK (MR/M01066X/1) (RR, DGR). KFM measurements were partly supported by the Austrian Science Fund (FWF) (project number P 31238-N28). IG was supported by at EPSRC doctoral training award, RL by a China Scholarship Council Cambridge Trust award, AP by a Raymond and Beverly Sackler Fund for Physics of Medicine, University of Cambridge, SBB by a Royal Society Newton Trust Fellowship and JC by the SENS Research Foundation. The electron microscopy was performed at the Cambridge Advanced Imaging Centre