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.
Highlights
Despite the crucial role of extracellular matrix (ECM) in directing cell fate in healthy and diseased tissues— in development, wound healing, tissue regeneration and cancer—the mechanisms that direct the assembly and regulate hierarchical architectures of ECM are poorly understood
Over the first 24 h, the fibroblasts cultured in the presence of ascorbic acid (Fig 2g–i) produced collagen fibres that co-localized with Fn fibrils
To gain insights into the mechanisms that enable the assembly of complex multi-component ECMs, we probed the tension-regulated interplay between Fn and collagen I fibres in ECM assembled by fibroblasts in cell culture
Summary
Despite the crucial role of extracellular matrix (ECM) in directing cell fate in healthy and diseased tissues— in development, wound healing, tissue regeneration and cancer—the mechanisms that direct the assembly and regulate hierarchical architectures of ECM are poorly understood. 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. Embryonic development and normal wound healing are characterized by the sequential deposition of multiple ECM proteins into a complex, ordered structure of interwoven fibrils[1,7]. Both fibronectin (Fn) and collagens are needed for normal embryo development[1,11]. Exogenously added soluble collagen I is known to organize into matrix fibres that co-localize with pre-existing Fn fibrils[32,33] These interactions involve collagen binding sites that are located on Fn’s N-terminus (Fig. 1) on modules FnI6, FnII1-2 and FnI7-9(refs 34–36). The presence of collagen I fibres and their specific molecular
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
