Dynamics of myristoylated amino-terminal domain of Src in the plasma membrane of mechano-stimulated cells studied by single molecule imaging

Src是机械力传导的关键信号分子。施加在细胞上的机械刺激可以诱导快速Src激活，但机械刺激如何激活Src分子在很大程度上仍然未知。在这里，我们观察到荧光标记的肉豆蔻酰化的氨基末端的Src在活细胞的质膜在单分子水平上检查的作用，其动力学和激活的氨基末端的Src的脂质部分。大多数探针被观察到在膜中迅速扩散，但显着部分的分子表现出时间固定。我们还发现，固定他们经常发生在附近的局灶性粘连（FA），这是机械和胆固醇依赖性。这些结果表明，Src的氨基末端的脂质部分可能发挥关键作用的动力学和激活的Src分子周围的脂肪酸通过与质膜的脂质微域的相互作用。

Src is a critical signaling molecule for mechanotransduction. Mechanical stimuli applied on the cell can induce a rapid Src activation, but it remains largely unknown how mechanical stimuli activates Src molecules. Here, we observed fluorescently labeled myristoylated amino terminus of Src in the plasma membrane of living cells at the single molecule level to examine the role of lipid moiety of the amino terminus of Src on its dynamics and activation. Most probes were observed to diffuse rapidly in the membrane, but that significant fraction of the molecules exhibited temporal immobilization. We also found that the immobilization of them occurred frequently in the proximity of focal adhesions (FAs), and that it was mechano- and cholesterol-dependent. These results suggest that lipid moiety of the amino terminus of Src may play a critical role in the dynamics and activation of Src molecules around FAs through the interaction with lipid micro domains of the plasma membrane.