Mechanosensation of cells is an important prerequisite for cellular function, e.g., in the context of cell migration, tissue organization, and morphogenesis. An important mechanochemical transducer is the actin cytoskeleton. In fact, previous studies have shown that actin cross-linkers such as α-actinin-4 exhibit mechanosensitive properties in their binding dynamics to actin polymers. However, to date, a quantitative analysis of tension-dependent binding dynamics in live cells is lacking. Here, we present a, to our knowledge, new technique that allows us to quantitatively characterize the dependence of cross-linking lifetime of actin cross-linkers on mechanical tension in the actin cortex of live cells. We use an approach that combines parallel plate confinement of round cells, fluorescence recovery after photobleaching, and a mathematical mean-field model of cross-linker binding. We apply our approach to the actin cross-linker α-actinin-4 and show that the cross-linking time of α-actinin-4 homodimers increases approximately twofold within the cellular range of cortical mechanical tension, rendering α-actinin-4 a catch bond in physiological tension ranges.

中文翻译：

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α-actinin-4 的结合动力学依赖于肌动蛋白皮质张力


细胞的机械感觉是细胞功能的重要先决条件，例如在细胞迁移、组织组织和形态发生的背景下。一种重要的机械化学传感器是肌动蛋白细胞骨架。事实上，之前的研究表明，α-actinin-4 等肌动蛋白交联剂在与肌动蛋白聚合物的结合动力学中表现出机械敏感性。然而，迄今为止，缺乏对活细胞中张力依赖性结合动力学的定量分析。在这里，据我们所知，我们提出了一种新技术，使我们能够定量表征肌动蛋白交联剂的交联寿命对活细胞肌动蛋白皮层机械张力的依赖性。我们使用的方法结合了圆形细胞的平行板限制、光漂白后的荧光恢复以及交联剂结合的数学平均场模型。我们将我们的方法应用于肌动蛋白交联剂 α-actinin-4，并表明 α-actinin-4 同二聚体的交联时间在皮质机械张力的细胞范围内增加了大约两倍，使 α-actinin-4 成为一个捕获物在生理张力范围内结合。