Arkhipov Sergey N, Maly Ivan V
Department of Computational Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Phys Biol. 2006 Oct 3;3(3):209-19. doi: 10.1088/1478-3975/3/3/006.
Directed secretion of cytotoxins or cytokines by T cells during immune response depends on migration of the centrosome in the T cell to the interface with the target cell. The mechanism of the centrosome translocation has been elusive. The presented computational analysis demonstrates that the centrosome should be positioned at the interface if the T cell attempts simultaneously (a) to minimize its surface area, (b) to maximize the interface area, (c) to maintain the cell volume and (d) to straighten the microtubules. Live three-dimensional microscopy and measurements show that the optimal position of the centrosome is achieved in large part (by about 40%) via rolling of the entire T cell body on the target surface; this movement appears to entrain the centrosome. The theoretical and experimental results draw attention to the previously unrecognized role of the whole-cell structure and whole-cell movements in the T cell polarization.
在免疫反应过程中,T细胞对细胞毒素或细胞因子的定向分泌取决于T细胞中的中心体向与靶细胞的界面迁移。中心体易位的机制一直难以捉摸。本文提出的计算分析表明,如果T细胞同时试图(a)最小化其表面积,(b)最大化界面面积,(c)维持细胞体积,以及(d)使微管变直,那么中心体应位于界面处。实时三维显微镜观察和测量结果表明,中心体的最佳位置很大程度上(约40%)是通过整个T细胞体在靶细胞表面滚动实现的;这种运动似乎带动了中心体。理论和实验结果使人们关注到全细胞结构和全细胞运动在T细胞极化中以前未被认识到的作用。