Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Biophys J. 2011 Dec 7;101(11):2620-8. doi: 10.1016/j.bpj.2011.09.022.
Dendritic cells (DCs) migrate from sites of inflammation to secondary lymphoid organs where they initiate the adaptive immune response. Although motility is essential to DC function, the mechanisms by which they migrate are not fully understood. We incorporated micropost array detectors into a microfluidic gradient generator to develop what we consider to be a novel method for probing low magnitude traction forces during directional migration. We found migration of primary murine DCs is driven by short-lived traction stresses at the leading edge or filopodia. The traction forces generated by DCs are smaller in magnitude than found in neutrophils, and of similar magnitude during chemotaxis and chemokinesis, at 18 ± 1.4 and 16 ± 1.3 nN/cell, respectively. The characteristic duration of local DC traction forces was 3 min. The maximum principal stress in the cell occurred in the plane perpendicular to the axis of motion, forward of the centroid. We illustrate that the spatiotemporal pattern of traction stresses can be used to predict the direction of future DC motion. Overall, DCs show a mode of migration distinct from both mesenchymal cells and neutrophils, characterized by rapid turnover of traction forces in leading filopodia.
树突状细胞 (DC) 从炎症部位迁移到次级淋巴器官,在那里它们启动适应性免疫反应。尽管运动对于 DC 功能至关重要,但它们迁移的机制尚未完全了解。我们将微孔阵列探测器整合到微流控梯度发生器中,开发了一种我们认为是探测定向迁移过程中低幅度牵引力的新方法。我们发现,原发性小鼠 DC 的迁移是由前缘或丝状伪足处短暂的牵引力驱动的。DC 产生的牵引力比中性粒细胞小,在趋化性和趋化运动中,牵引力分别为 18 ± 1.4 和 16 ± 1.3 nN/细胞。局部 DC 牵引力的特征持续时间为 3 分钟。细胞中的最大主应力发生在垂直于运动轴、质心前方的平面上。我们说明,牵引力的时空模式可用于预测 DC 未来运动的方向。总的来说,DC 的迁移模式与间充质细胞和中性粒细胞明显不同,其特征是前缘丝状伪足中的牵引力快速转换。