Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix

Kubow, K. E., Vukmirovic, R., Zhe, L., Klotzsch, E., Smith, M. L., Gourdon, D., Luna, S. and Vogel, V. (2015) Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix. Nature Communications, 6, 8026. (doi: 10.1038/ncomms9026) (PMID:26272817) (PMCID:PMC4539566)

Abstract

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.

• Item Type: Articles
• Additional Information: Financial support from the ETH Zurich, the Nanomedicine Center for Mechanobiology Directing the Immune Response (National Institutes of Health) Common Fund Nanomedicine Program (PN2 EY016586)), the European Research Council (Advanced Grant 233157, V.V.), the Volkswagen Stiftung (V.V.), and from the Human Frontier Science Program Organization (M.L.S.) are gratefully acknowledged.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gourdon, Professor Delphine
• Authors: Kubow, K. E., Vukmirovic, R., Zhe, L., Klotzsch, E., Smith, M. L., Gourdon, D., Luna, S., and Vogel, V.
• College/School: College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: Nature Communications
• Publisher: Nature Publishing Group
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2015 Macmillan Publishers Limited
• First Published: First published in Nature Communications 6(1):8026
• Publisher Policy: Reproduced under a Creative Commons License