Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix.
Despite the crucial role of extracellular matrix (ECM) in directing cell fate in healthy and diseased tissues--particularly in development, wound healing, tissue regeneration and cancer--the mechanisms that direct the assembly and regulate hierarchical architectures of ECM are poorly understood. Collagen I matrix assembly in vivo requires active fibronectin (Fn) fibrillogenesis by cells. Here we exploit Fn-FRET probes as mechanical strain sensors and demonstrate that collagen I fibres preferentially co-localize with more-relaxed Fn fibrils in the ECM of fibroblasts in cell culture. Fibre stretch-assay studies reveal that collagen I's Fn-binding domain is responsible for the mechano-regulated interaction. Furthermore, we show that Fn-collagen interactions are reciprocal: relaxed Fn fibrils act as multivalent templates for collagen assembly, but once assembled, collagen fibres shield Fn fibres from being stretched by cellular traction forces. Thus, in addition to the well-recognized, force-regulated, cell-matrix interactions, forces also tune the interactions between different structural ECM components.
1] Department of Biology, James Madison University, Harrisonburg, Virginia 22807, USA [2] Department of Health Sciences and Technology, ETH Zurich, CH-8093 Zürich, Switzerland.
Kristopher E
KE
Kubow
Department of Health Sciences and Technology, ETH Zurich, CH-8093 Zürich, Switzerland.
Radmila
R
Vukmirovic
Department of Health Sciences and Technology, ETH Zurich, CH-8093 Zürich, Switzerland.
Lin
L
Zhe
1] Department of Health Sciences and Technology, ETH Zurich, CH-8093 Zürich, Switzerland [2] Centre for Vascular Research, ARC Centre of Excellence in Advanced Molecular Imaging and Australian Centre for Nanomedicine, University of New South Wales, Sydney, New South Wales 2052, Australia.
Enrico
E
Klotzsch
1] Department of Health Sciences and Technology, ETH Zurich, CH-8093 Zürich, Switzerland [2] Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
Michael L
ML
Smith
1] Department of Health Sciences and Technology, ETH Zurich, CH-8093 Zürich, Switzerland [2] Department of Material Science and Engineering, Cornell University, Ithaca, New York 14853, USA.
Delphine
D
Gourdon
Department of Health Sciences and Technology, ETH Zurich, CH-8093 Zürich, Switzerland.
Sheila
S
Luna
Department of Health Sciences and Technology, ETH Zurich, CH-8093 Zürich, Switzerland.
Viola
V
Vogel
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001696:Biomechanical Phenomena; D024042:Collagen Type I / Q000502:physiology*; D005109:Extracellular Matrix; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000502:physiology*; D031541:Fluorescence Resonance Energy Transfer; D051379:Mice; D041681:NIH 3T3 Cells
D024042:Collagen Type I; D005353:Fibronectins; D001205:Ascorbic Acid