The dynamic dialogue between cells and matrices: Implications of fibronectin’s elasticity

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Abstract
The extracellular matrix (ECM) provides vital structure and organization to all metazoans, but it is far from an inanimate, unchanging assemblage of collagens, proteoglycans, and glycoproteins. ECM undergoes constant remodeling, most obviously during development, wound healing, and other repair processes. Defects in regulation of the deposition and turnover of ECM play important roles in pathological processes such as osteoporosis, atherosclerosis, arthritis, and fibrotic diseases. The deposition and remodeling of ECM is accomplished by cells, and the paper of Ohashi et al. in a recent issue of the Proceedings (1) provides some of the first observations of these processes in real time in living cell cultures. Ohashi et al. transfected cells with a chimera of green fluorescent protein and fibronectin (FN). FN is a prominent constituent of ECM around and beneath many cells, and FN-rich matrices provide substrates for cell adhesion and migration during development, wound healing, and other situations, as well as affecting many cellular functions including proliferation, survival, and differentiation (2). Ohashi et al. show that the FN–GFP chimera assembles into the FN-rich matrix surrounding their transfected cells, and they then use fluorescence microscopy to observe alterations in that matrix over time. This approach offers many opportunities for future research, but the observations they report already reveal some intriguing features that have implications not only for ECM structure and function but more widely in cell adhesion and beyond. Like most ECM proteins, FN is a large molecule; a dimer of subunits of around 250 kDa, each composed of a series of independently folding modular domains known as FN repeats I, II, and III; (12, 2, and 15–17 copies, respectively). Soluble dimeric FN molecules are loosely folded, rather like a string of beads clumped into a loose ball (Fig. 1a). In the ECM, these strings of beads are extended …