Utilizing Fibronectin Integrin-Binding Specificity to Control Cellular Responses

Abstract

Cells communicate with the extracellular matrix (ECM) protein fibronectin (Fn) through integrin receptors on the cell surface. Controlling integrin-Fn interactions offers a promising approach to directing cell behavior, such as adhesion, migration, and differentiation, as well as coordinated tissue behaviors such as morphogenesis and wound healing. Several different groups have developed recombinant fragments of Fn that can control epithelial to mesenchymal transition, sequester growth factors, and promote bone and wound healing. It is thought that these physiological responses are, in part, due to specific integrin engagement. Furthermore, it has been postulated that the integrin-binding domain of Fn is a mechanically sensitive switch that drives binding of one integrin heterodimer over another. Although computational simulations have predicted the mechano-switch hypothesis and recent evidence supports the existence of varying strain states of Fn , experimental evidence of the Fn integrin switch is still lacking. Evidence of the integrin mechano-switch will enable the development of new Fn-based peptides in tissue engineering and wound healing, as well as deepen our understanding of ECM pathologies, such as fibrosis.

Local remodeling of synthetic extracellular matrix microenvironments by co-cultured endometrial epithelial and stromal cells enables long-term dynamic physiological function

“…42–47 In order to identify peptides that foster the greatest degree of cell-matrix interactions in the initial stages of culture, we assessed attachment of stromal and epithelial cells to the surface of peptide-modified polyethylene glycol (PEG) hydrogels. Epithelial cells or stromal cells were seeded in serum-containing medium onto the surfaces of hydrogels synthesized by crosslinking 8-arm peptide-functionalized PEG macromers, fPEG-VS, with a dithiol MMP-sensitive peptide crosslinker, MMP-CL , as shown schematically in Figure 1A.…”

Tocotrienol alleviates inflammation and oxidative stress in a rat model of spinal cord injury via suppression of transforming growth factor-β

“…Siddiqui et al (21) reported that tocotrienol mitigates the damage of lipid-induced nephropathy through suppression of TGF-β and collagen type IV. Fibronectin is a multifunctional glycoprotein found in the extracellular matrix and plasma (35). Widely existing in animal tissues and tissue fluid, fibronectin is a V-shaped macromolecular glycoprotein with a molecular weight of ~450 kDa and a variety of biological activities (36).…”

Age‐specific function of α5β1 integrin in microglial migration during early colonization of the developing mouse cortex

“…In vitro adhesion of microglia to a fibronectin coated surface is regulated through fibronectin receptors, such as a5b1 integrin (Milner, 2009;Milner & Campbell, 2002aWelser-Alves, Boroujerdi, Tigges, & Milner, 2011). This integrin heterodimer is described as the major fibronectin receptor and is well characterized on the molecular as well as on the signaling level (Bachman, Nicosia, Dysart, & Barker, 2015;Hynes, 2002). To determine the expression of a5b1 integrin on embryonic microglia in vivo, E13.5, E15.5 and E17.5 cortices were isolated and the fibronectin receptor was immediately analyzed using flow cytometry.…”