近日，德国埃尔朗根-纽伦堡大学的Ben Fabry及其研究团队取得一项新进展。经过不懈努力，他们实现了三维生物聚合物基质中迁移免疫细胞的动态牵引力测量。相关研究成果已于2024年9月24日在国际知名学术期刊《自然—物理学》上发表。

本文介绍了一种方法，通过观察生物聚合物基质中的形变来测量快速迁移细胞在其中的动态牵引力。该方法考虑了三维组织基质的机械非线性，并可应用于共聚焦或明场图像堆栈的时间序列。它能够在广泛的力值和物体尺寸范围内实现精确的力重建，即使成像体积仅捕获了基质形变场的一小部分。

研究人员通过测量从轴突生长锥的约1纳牛顿力，到小鼠肠道类器官的约10微牛顿力的范围，展示了该方法的广泛适用性。研究发现，自然杀伤细胞表现出约50纳牛顿的大牵引力爆发，且随着基质刚度的增加而增强。这些力的爆发由肌球蛋白II的收缩力驱动，通过整合素β1粘附、局部粘附激酶和Rho激酶活性介导，并主要在细胞通过狭窄基质孔迁移时发生。

据悉，免疫细胞，例如自然杀伤细胞，能以每分钟数微米的高速度在致密组织中迁移。然而，这种迁移过程中牵引力的大小尚不清楚。

附：英文原文

Title: Dynamic traction force measurements of migrating immune cells in 3D biopolymer matrices

Author: Bhringer, David, Cndor, Mar, Bischof, Lars, Czerwinski, Tina, Gampl, Niklas, Ngo, Phuong Anh, Bauer, Andreas, Voskens, Caroline, Lpez-Posadas, Roco, Franze, Kristian, Budday, Silvia, Mark, Christoph, Fabry, Ben, Gerum, Richard

Issue&Volume: 2024-09-24

Abstract: 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 1nN for axon growth cones up to around 10μN for mouse intestinal organoids. We find that natural killer cells show bursts of large traction forces around 50nN that increase with matrix stiffness. These force bursts are driven by myosinII contractility, mediated by integrin β1 adhesions, focal adhesion kinase and Rho-kinase activity, and occur predominantly when the cells migrate through narrow matrix pores.

DOI: 10.1038/s41567-024-02632-8

Source: https://www.nature.com/articles/s41567-024-02632-8