Subcellular topography modulates actin dynamics and signaling in B-cells

亚细胞拓扑结构调节 B 细胞中的肌动蛋白动力学和信号传导

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作者:Christina M Ketchum, Xiaoyu Sun, Alexandra Suberi, John T Fourkas, Wenxia Song, Arpita Upadhyaya

Abstract

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.

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