scholarly journals Fibronectin Polymerization Regulates the Composition and Stability of Extracellular Matrix Fibrils and Cell-Matrix Adhesions

2002 ◽  
Vol 13 (10) ◽  
pp. 3546-3559 ◽  
Author(s):  
Jane Sottile ◽  
Denise C. Hocking

Remodeling of extracellular matrices occurs during development, wound healing, and in a variety of pathological processes including atherosclerosis, ischemic injury, and angiogenesis. Thus, identifying factors that control the balance between matrix deposition and degradation during tissue remodeling is essential for understanding mechanisms that regulate a variety of normal and pathological processes. Using fibronectin-null cells, we found that fibronectin polymerization into the extracellular matrix is required for the deposition of collagen-I and thrombospondin-1 and that the maintenance of extracellular matrix fibronectin fibrils requires the continual polymerization of a fibronectin matrix. Further, integrin ligation alone is not sufficient to maintain extracellular matrix fibronectin in the absence of fibronectin deposition. Our data also demonstrate that the retention of thrombospondin-1 and collagen I into fibrillar structures within the extracellular matrix depends on an intact fibronectin matrix. An intact fibronectin matrix is also critical for maintaining the composition of cell–matrix adhesion sites; in the absence of fibronectin and fibronectin polymerization, neither α5β1 integrin nor tensin localize to fibrillar cell–matrix adhesion sites. These data indicate that fibronectin polymerization is a critical regulator of extracellular matrix organization and stability. The ability of fibronectin polymerization to act as a switch that controls the organization and composition of the extracellular matrix and cell–matrix adhesion sites provides cells with a means of precisely controlling cell-extracellular matrix signaling events that regulate many aspects of cell behavior including cell proliferation, migration, and differentiation.

2011 ◽  
Vol 21 (04) ◽  
pp. 719-743 ◽  
Author(s):  
MARK A. J. CHAPLAIN ◽  
MIROSŁAW LACHOWICZ ◽  
ZUZANNA SZYMAŃSKA ◽  
DARIUSZ WRZOSEK

The process of invasion of tissue by cancer cells is crucial for metastasis — the formation of secondary tumours — which is the main cause of mortality in patients with cancer. In the invasion process itself, adhesion, both cell–cell and cell–matrix, plays an extremely important role. In this paper, a mathematical model of cancer cell invasion of the extracellular matrix is developed by incorporating cell–cell adhesion as well as cell–matrix adhesion into the model. Considering the interactions between cancer cells, extracellular matrix and matrix degrading enzymes, the model consists of a system of reaction–diffusion partial integro–differential equations, with nonlocal (integral) terms describing the adhesive interactions between cancer cells and the host tissue, i.e. cell–cell adhesion and cell–matrix adhesion. Having formulated the model, we prove the existence and uniqueness of global in time classical solutions which are uniformly bounded. Then, using computational simulations, we investigate the effects of the relative importance of cell–cell adhesion and cell–matrix adhesion on the invasion process. In particular, we examine the roles of cell–cell adhesion and cell–matrix adhesion in generating heterogeneous spatio-temporal solutions. Finally, in the discussion section, concluding remarks are made and open problems are indicated.


1995 ◽  
Vol 26 (10) ◽  
pp. 1114-1125 ◽  
Author(s):  
Jean-yves Scoazec ◽  
Jean-françois Flejou ◽  
Antonia D'errico ◽  
Anne Couvelard ◽  
Renata Kozyraki ◽  
...  

2021 ◽  
Author(s):  
Ana E. González Wusener ◽  
Ángela González ◽  
María E. Perez Collado ◽  
Melina R. Maza ◽  
Ignacio J. General ◽  
...  

Protein tyrosine phosphatase 1B (PTP1B) is an established regulator of cell-matrix adhesion and motility. However, the nature of substrate targets at adhesion sites remains to be validated. Here we used Bimolecular Fluorescence Complementation (BiFC) assays in combination with a substrate trapping mutant of PTP1B to directly examine whether relevant phosphotyrosines on paxillin and FAK are substrates of the phosphatase in the context of cell-matrix adhesion sites. We find that formation of catalytic complexes at cell-matrix adhesions requires intact tyrosine residues Y31 and Y118 on paxillin and the localization of the focal adhesion kinase (FAK) at adhesion sites. In addition, we find that PTP1B specifically targets the Y925 on the focal adhesion target (FAT) domain of FAK at adhesion sites. Electrostatic analysis indicates that dephosphorylation of this residue promotes the closed conformation of the FAT 4-helix bundle, and its interaction with paxillin at adhesion sites.


2002 ◽  
Vol 282 (1) ◽  
pp. H21-H29 ◽  
Author(s):  
Alan B. Moy ◽  
Ken Blackwell ◽  
Anant Kamath

We compared temporal changes in isometric tension in cultured human umbilical vein endothelial cells inoculated on a polymerized collagen membrane with changes in cell-cell and cell-matrix adhesion derived by a mathematical model of transendothelial cell resistance. Thrombin and histamine disrupt barrier function by targeting a greater loss in cell-cell adhesion, which preceded losses in overall transendothelial resistance. There were minor losses in cell-matrix adhesion, which was temporally slower than the decline in the overall transendothelial resistance. In contrast, thrombin and histamine restored barrier function by initiating a restoration of cell-matrix adhesion, which occurred before an increase in overall transendothelial resistance. Thrombin mediated a second and slower decline in cell-cell adhesion, which was not observed in histamine-treated cells. This decline in cell-cell adhesion temporally correlated with expressed maximal levels of tension development, suggesting that actin-myosin contraction directly strains cell-cell adhesion sites. Pretreatment of cells with ML-7 mediated more rapid recovery of cell-cell adhesion and had no effect on cell-matrix adhesion. Taken together, expression of actin-myosin contraction affects the restoration of barrier function by straining cell-cell adhesion sites.


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