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Terentjev, E.

Publications and source records attributed to Terentjev, E..

2 recordsLinked to original sources

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.

biophysics↗

Universal kinetics for engagement of mechanosensing pathways in cell adhesion

When plated onto substrates, cell morphology and even stem cell differentiation are influenced by the stiffness of their environment. Stiffer substrates give strongly spread (eventually polarized) cells with strong focal adhesions, and stress fibers; very soft substrates give a less developed cytoskeleton, and much lower cell spreading. The kinetics of this process of cell spreading is studied extensively, and important universal relationships are established on how the cell area grows with time. Here we study the population dynamics of spreading cells, investigating the characteristic processes involved in cell response to the substrate. We show that unlike the individual cell morphology, this population dynamics does not depend on the substrate stiffness. Instead, a strong activation temperature dependence is observed. Different cell lines on different substrates all have long-time statistics controlled by the thermal activation over a single energy barrier {triangleup}G {approx} 19 kcal/mol, while the early-time kinetics follows a power law ~ t5. This implies that the rate of spreading depends on an internal process of adhesion-mechanosensing complex assembly and activation: the operational complex must have 5 component proteins, and the last process in the sequence (which we believe is the activation of focal adhesion kinase) is controlled by the binding energy {triangleup}G.

biophysics↗