T lymphocytes utilize amoeboid migration to navigate effectively within complex microenvironments. The precise rearrangement of the actin cytoskeleton required for cellular forward propulsion is mediated by actin regulators, including the actin-related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates branched actin filaments at the leading edge. The consequences of modulating Arp2/3 activity on the biophysical properties of the actomyosin cortex and downstream T cell function are incompletely understood. We report that even a moderate decrease of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction in total F-actin content leads to reduced cortical tension and disrupted lamellipodia formation. Instead, in Arp3-knockdown cells, the motility mode is dominated by blebbing migration characterized by transient, balloon-like protrusions at the leading edge. Although this migration mode seems to be compatible with interstitial migration in three-dimensional environments, diminished locomotion kinetics and impaired cytotoxicity interfere with optimal T cell function. These findings define the importance of finely tuned, Arp2/3-dependent mechanophysical membrane integrity in cytotoxic effector T lymphocyte activities.

中文翻译：

---

肌动蛋白成核剂肌动蛋白相关蛋白2/3活性的部分丧失触发了原代T淋巴细胞的起泡。

T淋巴细胞利用类变形虫迁移在复杂的微环境中有效导航。细胞正向推进所需的肌动蛋白细胞骨架的精确重排由肌动蛋白调节剂介导，包括肌动蛋白相关蛋白2/3（Arp2 / 3）复合物，这是一种在前缘使分支的肌动蛋白丝成核的大分子机器。尚不完全了解调节Arp2 / 3活性对放线菌素皮质的生物物理特性和下游T细胞功能的影响。我们报告说，即使T细胞中Arp3水平的适度下降也会深刻影响肌动蛋白皮质的完整性。F-肌动蛋白总含量的减少导致皮质张力降低并破坏了片状脂蛋白形成。相反，在Arp3组合单元中，运动模式以气泡迁移为主，气泡迁移的特征是在前缘处出现短暂的气球状突起。尽管此迁移模式似乎与三维环境中的间质迁移兼容，但运动动力学降低和细胞毒性受损会干扰最佳T细胞功能。这些发现确定了微调的，依赖Arp2 / 3的机械物理膜完整性在细胞毒性效应T淋巴细胞活性中的重要性。