Contractile forces within the planar interface between T cell and antigen-presenting surface mechanically stimulate T cell receptors (TCR) in the mature immune synapses. However, the origin of mechanical stimulation during the initial, i.e., presynaptic, microvilli-based TCR activation in the course of immune surveillance remains unknown and new tools to help address this problem are needed. In this work, we develop nucleic acid nanoassembly (NAN)-based technology for functionalization of hydrogels using isothermal toehold-mediated reassociation of RNA/DNA heteroduplexes. Resulting platform allows for regulation with NAN linkers of 3D force momentum along the TCR mechanical axis, whereas hydrogels contribute to modulation of 2D shear modulus. By utilizing different lengths of NAN linkers conjugated to polyacrylamide gels of different shear moduli, we demonstrate an efficient capture of human T lymphocytes and tunable activation of TCR, as confirmed by T-cell spreading and pY foci.

T 细胞和抗原呈递表面之间的平面界面内的收缩力机械地刺激成熟免疫突触中的 T 细胞受体 (TCR)。然而，最初的机械刺激的起源，即在免疫监视过程中，突触前、基于微绒毛的 TCR 激活仍然未知，需要新的工具来帮助解决这个问题。在这项工作中，我们开发了基于核酸纳米组装 (NAN) 的技术，用于使用等温支架介导的 RNA/DNA 异源双链体的重新结合对水凝胶进行功能化。由此产生的平台允许使用 NAN 接头调节沿 TCR 机械轴的 3D 力动量，而水凝胶有助于调节 2D 剪切模量。通过利用与不同剪切模量的聚丙烯酰胺凝胶缀合的不同长度的 NAN 接头，我们证明了人类 T 淋巴细胞的有效捕获和 TCR 的可调激活，正如 T 细胞扩散和 pY 病灶所证实的那样。