The T cell receptor (TCR) is thought to be a mechanosensor, meaning that it transmits mechanical force to its antigen and leverages the force to amplify the specificity and magnitude of TCR signalling. Although a variety of molecular probes have been proposed to quantify TCR mechanics, these probes are immobilized on hard substrates, and thus fail to reveal fluid TCR–antigen interactions in the physiological context of cell membranes. Here we developed DNA origami tension sensors (DOTS) which bear force sensors on a DNA origami breadboard and allow mapping of TCR mechanotransduction at dynamic intermembrane junctions. We quantified the mechanical forces at fluid TCR–antigen bonds and observed their dependence on cell state, antigen mobility, antigen potency, antigen height and F-actin activity. The programmability of DOTS allows us to tether these to microparticles to mechanically screen antigens in high throughput using flow cytometry. Additionally, DOTS were anchored onto live B cells, allowing quantification of TCR mechanics at immune cell–cell junctions.

T 细胞受体 （TCR） 被认为是一种机械传感器，这意味着它将机械力传递到其抗原，并利用该力来放大 TCR 信号传导的特异性和强度。尽管已经提出了多种分子探针来量化 TCR 力学，但这些探针被固定在硬质基质上，因此无法揭示细胞膜生理环境中的流体 TCR-抗原相互作用。在这里，我们开发了 DNA 折纸张力传感器 （DOTS），它在 DNA 折纸面包板上装有力传感器，并允许在动态膜间连接处映射 TCR 机械转导。我们量化了流体 TCR-抗原键处的机械力，并观察了它们对细胞状态、抗原迁移率、抗原效力、抗原高度和 F-肌动蛋白活性的依赖性。DOTS 的可编程性使我们能够将它们与微粒相连，以使用流式细胞术以高通量机械筛选抗原。此外，DOTS 被锚定在活的 B 细胞上，可以定量免疫细胞-细胞连接处的 TCR 机制。