Abstract
The extracellular matrix (ECM) plays a key role as both structural scaffold and regulator of cell signal transduction in tissues. In times of ECM assembly and turnover, cells upregulate assembly of the ECM protein, fibronectin (FN). FN is assembled by cells into viscoelastic fibrils that can bind upward of 40 distinct growth factors and cytokines. These fibrils play a key role in assembling a provisional ECM during embryonic development and wound healing. Fibril assembly is also often upregulated during disease states, including cancer and fibrotic diseases. FN fibrils have unique mechanical properties, which allow them to alter mechanotransduction signals sensed and relayed by cells. Binding of soluble growth factors to FN fibrils alters signal transduction from these proteins, while binding of other ECM proteins, including collagens, elastins, and proteoglycans, to FN fibrils facilitates the maturation and tissue specificity of the ECM. In this review, we will discuss the assembly of FN fibrils from individual FN molecules; the composition, structure, and mechanics of FN fibrils; the interaction of FN fibrils with other ECM proteins and growth factors; the role of FN in transmitting mechanobiology signaling events; and approaches for studying the mechanics of FN fibrils.
Highlights
The extracellular matrix (ECM) plays a key role as both structural scaffold and regulator of cell signal transduction in tissues
A web woven of secreted fibrillar proteins, its protein composition is specific to tissue type, though two major structural themes have been identified: a thread-like interstitial network that is present between and around cells; and a pericellular sheet-like basement membrane that serves as a cellular platform and a boundary around cells [1,2,3]
Elastins, and PGs play a primarily structural role in the ECM. These proteins are either synthesized as precursor elements and crosslinked into their fibrillar structures by lysyl oxidase (LOX) or consist of peptide units covalently linked to carbohydrates that aggregate into enmeshed networks [4,5,6]
Summary
The extracellular matrix (ECM) is a substrate for cells that modulates migration, proliferation, differentiation, spreading and survival by serving as both a molecular reservoir and a structural scaffold with tissue-specific mechanical properties. A web woven of secreted fibrillar proteins, its protein composition is specific to tissue type, though two major structural themes have been identified: a thread-like interstitial network that is present between and around cells; and a pericellular sheet-like basement membrane that serves as a cellular platform and a boundary around cells [1,2,3] Despite their structural differences, fibrillar interstitial matrices and pericellular basement membranes share similarities in their initial assembly and overall composition and are constructed of four major protein classes: collagens, elastins, proteoglycans (PGs), and glycoproteins [1,2]. Elastins, and PGs play a primarily structural role in the ECM These proteins are either synthesized as precursor elements (procollagen, tropoelastin) and crosslinked into their fibrillar structures by lysyl oxidase (LOX) or consist of peptide units covalently linked to carbohydrates that aggregate into enmeshed networks [4,5,6]. FN molecules contain multiple domains that bind several ECM proteins, growth factors, and small molecules, it has become evident that the understanding of assembly, molecular storage, and cellular interaction within the ECM is dependent on the understanding of FN fibril assembly and its interaction with cells, other ECM proteins, and soluble signaling proteins [1,13]
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