Askari Shohreh, Saldo Rubio Guillem, Datar Anagha, Harjunpää Heidi, Fagerholm Susanna C, Backholm Matilda
Department of Applied Physics, Aalto University, Espoo, Finland.
Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
J R Soc Interface. 2025 Jul;22(228):20250231. doi: 10.1098/rsif.2025.0231. Epub 2025 Jul 23.
T-cells are a crucial subset of white blood cells that play a central role in the immune system. When T-cells bind antigens, it leads to cell activation and the induction of an immune response. If T-cells are activated by antigens or artificially they form multicellular aggregates. The mechanical properties of such clusters provide valuable information on different T-cell activation pathways. Furthermore, the aggregate mechanics capture how T-cells are affected by mechanical forces and interact within larger conglomerates, such as lymph nodes and tumours. However, an understanding of collective T-cell adhesion and mechanics following cell activation is currently lacking. Probing the mechanics of fragile and microscopically small living samples is experimentally challenging. Here, the micropipette force sensor technique was used to stretch T-cell aggregates and directly measure their Young's modulus and ultimate tensile strength. A mechanistic model was developed to correlate how the stiffness of the mesoscale multicellular aggregate emerges from the mechanical response of the individual microscopic cells within the cluster. We show how the aggregate elasticity is affected by different activators and relate this to different activation pathways in the cells. Our soft matter mechanics study of multicellular T-cell aggregates contributes to our understanding of the biology behind immune cell activation.
T细胞是白细胞的一个关键亚群，在免疫系统中起着核心作用。当T细胞结合抗原时，会导致细胞活化并引发免疫反应。如果T细胞被抗原激活或人工激活，它们会形成多细胞聚集体。此类聚集体的力学特性为不同的T细胞活化途径提供了有价值的信息。此外，聚集体力学揭示了T细胞如何受到机械力的影响以及在诸如淋巴结和肿瘤等更大的聚集体中的相互作用。然而，目前尚缺乏对细胞活化后集体T细胞黏附力和力学的理解。探测脆弱且微观尺寸小的活体样本的力学特性在实验上具有挑战性。在此，使用微量移液器力传感器技术拉伸T细胞聚集体，并直接测量其杨氏模量和极限抗拉强度。开发了一个力学模型，以关联中尺度多细胞聚集体的刚度如何从聚集体内单个微观细胞的力学响应中产生。我们展示了聚集体弹性如何受到不同激活剂的影响，并将其与细胞中的不同活化途径相关联。我们对多细胞T细胞聚集体的软物质力学研究有助于我们理解免疫细胞活化背后的生物学机制。
