Subcellular topography modulates actin dynamics and signaling in B-cells.
Subcellular topography modulates actin dynamics and signaling in B-cells.
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DOI：
10.1091/mbc.e17-06-0422
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发表时间：
2018-07-15
影响因子：
3.3
通讯作者：
Upadhyaya A
中科院分区：
文献类型：
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作者：
Ketchum CM;Sun X;Suberi A;Fourkas JT;Song W;Upadhyaya A
b细胞信号激活是由b细胞受体（bcr）与膜结合抗原的结合最有效地触发的。在体内，b细胞在抗原呈递细胞（APC）上遇到抗原，APC具有复杂的表面和卷曲的拓扑结构，流体膜和可变形的细胞体。然而，抗原呈递的物理性质是否以及如何影响b细胞活化尚不清楚。在这里，我们使用纳米形貌表面，允许几何参数的系统变化，以显示亚细胞尺度上的表面特征影响b细胞信号传导和肌动蛋白动力学。间距为3微米或更大的平行纳米脊在细胞腹侧表面诱导肌动蛋白强度振荡。纳米形貌诱导的肌动蛋白动力学需要BCR信号、肌动蛋白聚合和肌球蛋白收缩性。刺激表面的地形也调节BCR簇在活化b细胞中的分布。最后，在纳米图案表面上刺激的b细胞表现出细胞内钙振荡，其频率取决于地形。我们的研究结果指出了配体呈现的物理方面的重要性，特别是纳米形貌对b细胞活化和抗原聚集的重要性。
B-cell signaling activation is most effectively triggered by the binding of B-cell receptors (BCRs) to membrane-bound antigens. In vivo, B-cells encounter antigen on antigen-presenting cells (APC), which possess complex surfaces with convoluted topographies, a fluid membrane and deformable cell bodies. However, whether and how the physical properties of antigen presentation affect B-cell activation is not well understood. Here we use nanotopographic surfaces that allow systematic variation of geometric parameters to show that surface features on a subcellular scale influence B-cell signaling and actin dynamics. Parallel nanoridges with spacings of 3 microns or greater induce actin intensity oscillations on the ventral cell surface. Nanotopography-induced actin dynamics requires BCR signaling, actin polymerization, and myosin contractility. The topography of the stimulatory surface also modulates the distribution of BCR clusters in activated B-cells. Finally, B-cells stimulated on nanopatterned surfaces exhibit intracellular calcium oscillations with frequencies that depend on topography. Our results point to the importance of physical aspects of ligand presentation, in particular, nanotopography for B-cell activation and antigen gathering.