title: Utilizing Fibronectin Integrin-Binding Specificity to Control Cellular Responses.
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 Fnin 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.
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia .
authors.forename: Haylee
authors.initials: H
authors.lastname: Bachman
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology , Atlanta, Georgia .
authors.forename: John
authors.initials: J
authors.lastname: Nicosia
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology , Atlanta, Georgia .
authors.forename: Marilyn
authors.initials: M
authors.lastname: Dysart
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia . ; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology , Atlanta, Georgia . ; The Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology , Atlanta, Georgia .
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Barker