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• W2270659359 startingPage "e0139959" @default.
• W2270659359 abstract "Cells can sense forces applied to them, but also the stiffness of their environment. These are two different phenomena, and here we investigate the mechanosensitivity of the IInd kind: how the cell can measure an elastic modulus at a single point of adhesion -- and how the cell can receive and interpret the chemical signal released from the sensor. Our model uses the example of large latent complex of TGFb as a sensor. Stochastic theory gives the rate of breaking of latent complex, which initiates the signaling feedback loop after the active TGFb release and leads to a change of cell phenotype driven by the smooth muscle actin. We investigate the dynamic and steady-state behaviours of the model, comparing them with experiments. In particular, we analyse the timescale of approach to the steady state, the stability of the non-linear dynamical system, and how the steady-state concentrations of the key markers vary depending on the elasticity of the substrate. We discover a crossover region for values of substrate elasticity closely corresponding to that of the fibroblast to myofibroblast transition. We suggest that the cell could actively vary the parameters of its dynamic feedback loop to `choose' the position of the transition region and the range of substrate elasticity that it can detect. In this way, the theory offers the unifying mechanism for a variety of phenomena, such as the myofibroblast conversion in fibrosis of wounds and lungs and smooth muscle cell dysfunction in cardiac disease." @default.
• W2270659359 created "2016-06-24" @default.
• W2270659359 creator A5014104707 @default.
• W2270659359 creator A5062696138 @default.
• W2270659359 creator A5088132879 @default.
• W2270659359 date "2015-10-08" @default.
• W2270659359 modified "2023-09-27" @default.
• W2270659359 title "Mechanosensitivity of the 2nd Kind: TGF-β Mechanism of Cell Sensing the Substrate Stiffness" @default.
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• W2270659359 doi "https://doi.org/10.1371/journal.pone.0139959" @default.
• W2270659359 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4598016" @default.
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• W2270659359 hasPublicationYear "2015" @default.
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