Nanotopography modulates cytoskeletal organization and dynamics during T cell activation.
Nanotopography modulates cytoskeletal organization and dynamics during T cell activation.
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DOI：
10.1091/mbc.e21-12-0601
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发表时间：
2022-09-01
影响因子：
3.3
通讯作者：
Upadhyaya, Arpita
中科院分区：
文献类型：
--
作者：
Wheatley, Brittany A.;Rey-Suarez, Ivan;Hourwitz, Matt J.;Kerr, Sarah;Shroff, Hari;Fourkas, John T.;Upadhyaya, Arpita
暴露于抗原提呈细胞(APC)表面的MHC抗原复合体可激活T细胞，诱导免疫突触(IS)的形成。因此，APC表面的抗原检测是获得性免疫反应的关键步骤。T细胞在体内遇到的抗原提呈表面的物理性质被认为调节了T细胞的激活和增殖。虽然刚性和配体迁移率的影响是形成，但复杂的表面形貌对这一过程的影响还不是很清楚。在这里，我们使用高分辨率荧光显微镜，在具有不同间距的平行纳米脊的纳米碎片表面上，研究纳米拓扑术如何在T细胞激活的早期阶段调节细胞骨架的动力学和信号。我们发现，尽管与平面上的细胞相比，纳米脊减少了最大铺展面积，但脊状突起增强了肌动蛋白和信号激酶ZAP-70在IS的积累。肌动蛋白聚合在脊线的存在时更具动力，这影响了肌动蛋白流动的方向性和微管(MT)的生长。我们的结果表明，激活表面的地形既影响T细胞的整体形态，也影响肌动蛋白和MT动力学的局部变化，共同影响T细胞信号转导。
Exposure to MHC-antigen complexes on the surface of antigen-presenting cells (APCs) activates T cells, inducing the formation of the immune synapse (IS). Antigen detection at the APC surface is thus a critical step in the adaptive immune response. The physical properties of antigen-presenting surfaces encountered by T cells in vivo are believed to modulate T cell activation and proliferation. Although stiffness and ligand mobility influence IS formation, the effect of the complex topography of the APC surface on this process is not well understood. Here we investigate how nanotopography modulates cytoskeletal dynamics and signaling during the early stages of T cell activation using high-resolution fluorescence microscopy on nanofabricated surfaces with parallel nanoridges of different spacings. We find that although nanoridges reduce the maximum spread area as compared with cells on flat surfaces, the ridges enhance the accumulation of actin and the signaling kinase ZAP-70 at the IS. Actin polymerization is more dynamic in the presence of ridges, which influence the directionality of both actin flows and microtubule (MT) growth. Our results demonstrate that the topography of the activating surface exerts both global effects on T cell morphology and local changes in actin and MT dynamics, collectively influencing T cell signaling.
影响因子：
3.7
作者：
Kwon KW;Park H;Doh J
通讯作者：
Doh J
影响因子：
3.7
作者：
Yu CH;Wu HJ;Kaizuka Y;Vale RD;Groves JT
通讯作者：
Groves JT