Development of nascent focal adhesions in spreading cells

Cell spreading provides one of the simplest configurations in which eukaryotic cells develop angular symmetry-breaking assemblies of mechanosensing and mechanotransducive organelles in preparation for cell differentiation and movement. By identifying the edge of the cell-ECM adhesion area as having an important role in mechanosensor complex aggregation, we consider the spatial patterns arising on this edge, within a 1D lattice model of the nearest-neighbour interaction between individual integrin-mediated mechanosensors. We obtain the Ginzburg-Landau free energy for this model and analyse the spectrum of spatial modes as the cell spreads and increases the contact area. We test the plausibility of our model by comparing its predictions for the azimuthal angular frequency of aggregation of mechanosensors into nascent focal adhesions (FAs) to observations of the paxillin distribution in spreading fibroblasts. STATEMENT OF SIGNIFICANCEThe topic of cell adhesion on substrates is very active, with numerous theoretical, experimental and computer simulation studies probing the mechanisms and signalling pathways of cell response to interacting with substrate. Integrin-based adhesion complexes are known to be the individual units of this process, and their dense aggregation into focal adhesions leads to cells developing asymmetry, polarity, and eventually - locomotion. Here we develop a theoretical model that suggests that physical interactions between individual adhesion complexes is the factor that defines the initial breaking of symmetry of the cell spreading on substrate, and predicts the characteristic wavelength of modulation above the critical size of adhesion area.