Focal adhesion points

The integrins do not have any enzyme activity in their own cytoplasmic domain, but on hgand binding, stimulation of tyrosine phosphorylation is observed on the cytoplasmic side of many cells, such as fibroblasts and platelets. The exact configuration of protein-protein interactions on the cytosolic side of the integrins is not clear and the mechanism of stimulation of protein tyrosine kinases is unknown. Some components of the focal adhesion points, such as the structural protein tensin, have SH2 and SH3 domains that may serve as specific attachment points for tyrosine kinases and other signal proteins. 

By bringing together two signaling proteins at the same site of the cell (e.g., in focal adhesion points of the cell membrane) an efficient communication between the pro-... 

Nanotopography may provide superior biomimetic cell-modulating cues, as it may further resemble the natural ECM environment in which cells reside and interact. It has been shovra that nanopattemed surfaces can improve protein adsorption and cellular response, since as on rougher surfaces, the focal adhesion points are located at cell edges, where the contact with the materials surface takes place [61,71-77]. 

Integrins are a family of transmembrane heterodimeric glycoproteins that are receptors for specific epitopes of extracellular matrix proteins and for other cell-surface molecules (Kramer et al, 1993). Integrins exist as a dimer complex composed of an a-subunit (120-180 kD) noncovalently associated with a /1-subunit (90-110 kD) (Hynes, 1992). At least 8 /1-subunits and 14 -units have been identified and are concentrated at loci, called focal adhesion sites, of close proximity between cells and extracellular matrices on substrates (Hynes, 1992). Focal adhesion sites are points of aggregation of, and are physically associated with, intracellular cytoskeletal molecules that control, direct, and modulate cell function in response to extracellular signals (Schwartz, 1992). 

In the CNS, there is also a radial component formed by points of focal adhesion between sheaths which helps maintain CNS myelin integrity. 

Although all these processes are connected in one way or another with the cytoskeleton, how the rearrangement of the cytoskeleton is actually related to the response of cells to signals controlling cell polarity, cell movement, cell adhesion, and cell division is not known. These complex processes are not yet fully understood, but it seems that the point of control of Rho/Rac/Cdc42 is a phosphorylation cascade, where integrin and the focal adhesion kinase (FAK), and cytosolic Src kinases, play a central role. 

A specialized cell-matrix contact point, which is stracturaUy distinct from focal adhesion complexes. See Linder, S. and Aepfelbacher, M., Podo-somes adhesion hot-spots of invasive cells. Trends Cell Biol. 13, 376-385, 2003 McNiver, M.A., Baldassarre, M., and Buccione, R., The role of dynamin in the assembly and function of podosomes and invadopodia. Front. Biosci. 9, 1944-1953, 2004 Linder, S., and Kopp, R, Podosomes at a glance, J. Cell Sci. 118, 2079-2082, 2005. 

Fig. 5 Shape and contractility of adherent cells. A circular cell (a) and an elliptical cell (c) with adhesion points along the boundary. The angular coordinates 0 of the focal adhesions are measured in the anti-clockwise direction as shown in subplot (a). Forces measured at the focal adhesions as a function of 0 are shown in (b) for the circular cell and in (d) for the elliptical cell. Data points are obtained from the simulation and bold lines are the best fits, -ve sign of force represents inward pull. In the circular cell, the force is uniform throughout the cytoskeletal network, whereas, in the elliptical cell, elongated shape breaks the uniform force distribution. Highly stressed regions develop along the boundary around p2, p4, p6 and p8 and stresses remain low around pi, p3, p5 and p7.

Gooding JM, Yap KL, Ikura M. The cadherin-catenin complex as a focal point of cell adhesion and signalling New insights from three-dimensional structures. Bioessays. 2004 26 497-511. 

The focal point of work on solid oxide fuel cells during this period was the development of electrode materials. An early problem was poor adhesion of the anode layers, which became obvious in 1963 [59]. Spacil as early as 1964 found the now well-known solution of using layers of nickel closely mixed with solid electrolyte material [101]. 

---