Integrins clustering with

Fak (focal adhesion kinase) is expressed in most tissues and is evolutionary conserved across species. It is activated by integrin clustering and by stimulation of several G protein-coupled recqrtors and RTKs. Fak is associated with focal adhesions and regulates cell spreading and migration. The kinase is essential for embryonic development since the homozygote Fak knockout is embryonic lethal. Pyk2 (proline-rich tyrosine kinase 2), the second member of the Fak kinase family has a more restricted expression pattern (primarily neuronal and hematopoietic cells) and does not localize to focal adhesions. 

Integrins associate with the membrane protein caveolin.34 Although little is yet known about this particular interaction, it could assist in forming integrin clusters at the plasma membrane which might serve as a scaffold for the assembly of multi-component signalling complexes. This possibility is attractive, because caveolin binds cholesterol and glycosphingolipids and forms membrane rafts , enriched in myristoylated and palmitoy-lated Src-family kinases (Chapter 8).35... 

Integrins cluster into adhesive structures with various morphologies in nonepithelial cells. Immunofluorescence methods were used to detect adhesive structures (green) on cultured cells. 

FIGURE 5.8 Scheme for the control of cell s integrin clustering at nanostructured and biofunctionalized substrates (based on spatially defined deposition of gold nanodots through block copolymer lithography). Source Adapted from Arnold et al. [17], figure 2. Reproduced with permission from John Wiley Sons. 

In a first experiment with fibroblasts in culture, an extended 73-nm-spaced pattern was compared with a 2-pm-patterned 58-nm array. Although the total nanoparticle density of the micropatterned surface was considerably lower than that of the homogeneously coated one, the cells could only form FAs on 58-nm-spaced RGD motives. It is thus obvious that integrin function critically depends on the spatial confinement of integrins to favour clustering but not on the total number of bound integrins [82],... 

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