Immune cells, such as natural killer cells, migrate with high speeds of several micrometres per minute through dense tissue. However, the magnitude of the traction forces during this migration is unknown. Here we present a method to measure dynamic traction forces of fast migrating cells in biopolymer matrices from the observed matrix deformations. Our method accounts for the mechanical nonlinearity of the three-dimensional tissue matrix and can be applied to time series of confocal or bright-field image stacks. It allows for precise force reconstruction over a wide range of force magnitudes and object sizes—even when the imaged volume captures only a small part of the matrix deformation field. We demonstrate the broad applicability of our method by measuring forces from around 1 nN for axon growth cones up to around 10 μN for mouse intestinal organoids. We find that natural killer cells show bursts of large traction forces around 50 nN that increase with matrix stiffness. These force bursts are driven by myosin II contractility, mediated by integrin β1 adhesions, focal adhesion kinase and Rho-kinase activity, and occur predominantly when the cells migrate through narrow matrix pores.

免疫细胞，例如自然杀伤细胞，以每分钟几微米的高速迁移穿过致密组织。然而，迁移过程中牵引力的大小尚不清楚。在这里，我们提出了一种根据观察到的基质变形来测量生物聚合物基质中快速迁移细胞的动态牵引力的方法。我们的方法考虑了三维组织基质的机械非线性，并且可以应用于共焦或明场图像堆栈的时间序列。即使成像体积仅捕获矩阵变形场的一小部分，它也可以在各种力大小和物体尺寸上进行精确的力重建。我们通过测量从轴突生长锥约 1 nN 到小鼠肠道类器官约 10 μN 的力，证明了我们的方法的广泛适用性。我们发现自然杀伤细胞表现出约 50 nN 的大牵引力，该牵引力随着基质硬度的增加而增加。这些力爆发由肌球蛋白 II 收缩性驱动，由整合素 β1 粘附、粘着斑激酶和 Rho 激酶活性介导，并且主要在细胞迁移通过狭窄的基质孔时发生。