Focal Adhesion Kinase: The Reversible Molecular Mechanosensor
Focal Adhesion Kinase: The Reversible Molecular Mechanosensor
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DOI：
10.1016/j.bpj.2017.04.048
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发表时间：
2017-06-06
影响因子：
3.4
通讯作者：
Terentjev, Eugene M.
中科院分区：
文献类型：
--
作者：
Bell, Samuel;Terentjev, Eugene M.
传感器是控制细胞对环境反应的途径的第一个元素。对机械刺激产生或产生化学信号的蛋白质复合物被称为“机械传感器”。在这项工作中，我们建立了一个描述可逆单分子刚度传感器物理机制的理论模型。虽然这具有普遍应用的潜力，但这里我们将该模型应用于局灶黏附激酶，它在其活性磷酸化构象中启动化学信号，但可以自发地返回到其封闭折叠构象。我们发现构象变化的速率如何取决于基底刚度和细胞骨架施加的拉力。我们发现传感器是稳态的，自发地自我调节，以达到其最大灵敏度范围与衬底刚度相匹配的状态。结果与不同底物上细胞的表型观察结果比较好。
Sensors are the first element of the pathways that control the response of cells to their environment. Protein complexes that produce or enable a chemical signal in response to a mechanical stimulus are called "mechanosensors". In this work, we develop a theoretical model describing the physical mechanism of a reversible single-molecule stiffness sensor. Although this has the potential for general application, here we apply the model to focal adhesion kinase, which initiates the chemical signal in its active phosphorylated conformation, but can spontaneously return to its closed folded conformation. We find how the rates of conformation changes depend on the substrate stiffness and the pulling force applied from the cell cytoskeleton. We find the sensor is homeostatic, spontaneously self-adjusting to reach a state where its range of maximum sensitivity matches the substrate stiffness. The results compare well with the phenotype observations of cells on different substrates.