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Collagen Fibril Ultrastructure in Mice Lacking Discoidin Domain Receptor 1

Published online by Cambridge University Press:  22 June 2016

Jeffrey R. Tonniges ,
Benjamin Albert ,
Edward P. Calomeni ,
Shuvro Roy ,
Joan Lee ,
Xiaokui Mo ,
Susan E. Cole  and
Gunjan Agarwal
Jeffrey R. Tonniges
Affiliation:
Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA
Benjamin Albert
Affiliation:
Biomedical Engineering Department, The Ohio State University, Columbus, OH 43210, USA
Edward P. Calomeni
Affiliation:
Department of Pathology, The Ohio State University, Columbus, OH 43210, USA
Shuvro Roy
Affiliation:
David Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
Joan Lee
Affiliation:
David Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
Xiaokui Mo
Affiliation:
Center for Biostatistics, The Ohio State University, Columbus, OH 43210, USA
Susan E. Cole
Affiliation:
Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA
Gunjan Agarwal*
Affiliation:
Biomedical Engineering Department, The Ohio State University, Columbus, OH 43210, USA David Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
*
*Corresponding author. [email protected]
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Abstract

The quantity and quality of collagen fibrils in the extracellular matrix (ECM) have a pivotal role in dictating biological processes. Several collagen-binding proteins (CBPs) are known to modulate collagen deposition and fibril diameter. However, limited studies exist on alterations in the fibril ultrastructure by CBPs. In this study, we elucidate how the collagen receptor, discoidin domain receptor 1 (DDR1) regulates the collagen content and ultrastructure in the adventitia of DDR1 knock-out (KO) mice. DDR1 KO mice exhibit increased collagen deposition as observed using Masson’s trichrome. Collagen ultrastructure was evaluated in situ using transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Although the mean fibril diameter was not significantly different, DDR1 KO mice had a higher percentage of fibrils with larger diameter compared with their wild-type littermates. No significant differences were observed in the length of D-periods. In addition, collagen fibrils from DDR1 KO mice exhibited a small, but statistically significant, increase in the depth of the fibril D-periods. Consistent with these observations, a reduction in the depth of D-periods was observed in collagen fibrils reconstituted with recombinant DDR1-Fc. Our results elucidate how DDR1 modulates collagen fibril ultrastructure in vivo, which may have important consequences in the functional role(s) of the underlying ECM.

Keywords

collagenaortadiscoidin domain receptor 1electron microscopyatomic force microscopy
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 22 , Issue 3 , June 2016 , pp. 599 - 611
Copyright
Copyright © Microscopy Society of America 2016

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