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Review
. 2015 Aug 1;4(8):501-511.
doi: 10.1089/wound.2014.0621.

Utilizing Fibronectin Integrin-Binding Specificity to Control Cellular Responses

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Free PMC article
Review

Utilizing Fibronectin Integrin-Binding Specificity to Control Cellular Responses

Haylee Bachman et al. Adv Wound Care (New Rochelle). .
Free PMC article

Abstract

Significance: 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. Recent Advances: 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. Critical Issues: Although computational simulations have predicted the mechano-switch hypothesis and recent evidence supports the existence of varying strain states of Fn in vivo, experimental evidence of the Fn integrin switch is still lacking. Future Directions: 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.

Figures

None
Thomas H. Barker, PhD
<b>Figure 1.</b>
Figure 1.
Modular structure of fibronectin. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound
<b>Figure 2.</b>
Figure 2.
Proposed model of FnIII domain unfolding by Erickson in 1994. As tension is applied to the relaxed molecule (A), the domains first align (B), followed by unfolding of certain domains (C). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound
<b>Figure 3.</b>
Figure 3.
SMD simulation of early stages of FNIII10 unfolding under force. RGD loop is shown in red between the F and G strands. As the G strand of FnIII10 (shown in (A)) is pulled (B), the RGD loop is brought closer to the bulk of the module (C). SMD, steered molecular dynamics. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

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