Fibronectin and Integrins in Cell Adhesion, Signaling, and Morphogenesis

Abstract

Fibronectin and integrins play crucial roles in a variety of morphogenetic processes, in which they mediate cell adhesion, migration, and signal transduction. They induce hierarchical transmembrane organization of cytoskeletal and signaling molecules into multimolecular complexes of more than 30 proteins. Organization of these complexes is a synergistic process dependent on integrin aggregation and occupancy, as well as tyrosine phosphorylation. Integrins also cooperate with growth-factor receptors to enhance signaling. Fibronectin and integrins induce a variety of downstream effects, including enhanced transcription factor activity, induction of over 30 genes (> half novel), and altered expression of over 100 proteins. Fibronectin and integrins therefore trigger a hierarchy of signaling responses involved in regulating processes crucial for normal morphogenesis, including cell adhesion, migration, and specific gene expression.

Improved growth factor directed vascularization into fibrin constructs through inclusion of additional extracellular molecules

“…Fibronectin is a large dimeric protein that is found in early to mid stages of wound healing ECMs and it contains numerous cell-and ECM protein-binding moieties (Gailit and Clark, 1994;Magnusson and Mosher, 1998;Miyamoto et al, 1998;Potts and Campbell, 1996). Additionally, fibronectin can act as a depot for some growth factors (Gailit and Clark, 1994).…”

Fibronectin's Central Cell-binding Domain Supports Focal Adhesion Formation and Rho Signal Transduction

“…It interacts with multiple cell surface receptors and plays an important role in the regulation of anchorage-dependent cell growth, cell migration, differentiation, gene expression, tumor development and metastasis, embryogenesis, angiogenesis, and wound healing (1)(2)(3)(4)(5)(6). Cell adhesion to the immobilized FN leads to clustering of the integrins and accumulation of multiple cytoskeletal and signaling proteins around the integrin cytoplasmic domain.…”

Biomaterials for spinal cord repair

“…Unlike some other ECM proteins, fibronectin does not undergo spontaneous polymerization, but rather does so via a highly-regulated, cell-mediated process [58] . The biological activity of fibronectin is mediated by RGD-integrin α5β1 binding, and also has an additional integrin-binding site [59] , PHRSN [60,61] , that results in a synergistic effect on cell adhesion and the activation of a variety of pathways leading to changes in >30 genes [59] .…”

“…Unlike some other ECM proteins, fibronectin does not undergo spontaneous polymerization, but rather does so via a highly-regulated, cell-mediated process [58] . The biological activity of fibronectin is mediated by RGD-integrin α5β1 binding, and also has an additional integrin-binding site [59] , PHRSN [60,61] , that results in a synergistic effect on cell adhesion and the activation of a variety of pathways leading to changes in >30 genes [59] .Although incapable of forming a hydrogel on its own, as a potential treatment strategy, it has been used in combination with hydrogels for spinal cord repair due to its cell-signaling properties through RGD-integrin binding [62] .After injury, it has been shown to elicit neurite outgrowth [57] .Fibronectin may be most relevant for regenerating damaged blood vessels via the α5β1 integrin receptor, which in turn could improve nutrient delivery to cells and reduce the infiltration of circulating macrophages following SCi [63] . Fibronectin has also been used in biosynthetic conduits for regeneration in a complete spinal transection model [64] .…”