Sniadecki Nathan J, Anguelouch Alexandre, Yang Michael T, Lamb Corinne M, Liu Zhijun, Kirschner Stuart B, Liu Yaohua, Reich Daniel H, Chen Christopher S
Department of Bioengineering, University of Pennsylvania, 510 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14553-8. doi: 10.1073/pnas.0611613104. Epub 2007 Sep 5.
Cells respond to mechanical forces whether applied externally or generated internally via the cytoskeleton. To study the cellular response to forces separately, we applied external forces to cells via microfabricated magnetic posts containing cobalt nanowires interspersed among an array of elastomeric posts, which acted as independent sensors to cellular traction forces. A magnetic field induced torque in the nanowires, which deflected the magnetic posts and imparted force to individual adhesions of cells attached to the array. Using this system, we examined the cellular reaction to applied forces and found that applying a step force led to an increase in local focal adhesion size at the site of application but not at nearby nonmagnetic posts. Focal adhesion recruitment was enhanced further when cells were subjected to multiple force actuations within the same time interval. Recording the traction forces in response to such force stimulation revealed two responses: a sudden loss in contractility that occurred within the first minute of stimulation or a gradual decay in contractility over several minutes. For both types of responses, the subcellular distribution of loss in traction forces was not confined to locations near the actuated micropost, nor uniformly across the whole cell, but instead occurred at discrete locations along the cell periphery. Together, these data reveal an important dynamic biological relationship between external and internal forces and demonstrate the utility of this microfabricated system to explore this interaction.
细胞会对机械力产生反应,无论这种力是外部施加的还是通过细胞骨架在内部产生的。为了单独研究细胞对力的反应,我们通过微制造的磁性柱向细胞施加外力,这些磁性柱包含散布在一系列弹性柱阵列中的钴纳米线,弹性柱充当细胞牵引力的独立传感器。磁场在纳米线中感应出扭矩,使磁性柱发生偏转,并将力施加到附着在阵列上的细胞的单个黏附点上。利用这个系统,我们研究了细胞对施加力的反应,发现施加阶跃力会导致施加部位局部黏着斑大小增加,但附近的非磁性柱处则不会。当细胞在同一时间间隔内受到多次力驱动时,黏着斑的募集会进一步增强。记录对这种力刺激的牵引力揭示了两种反应:一种是在刺激的第一分钟内发生的收缩性突然丧失,另一种是在几分钟内收缩性逐渐衰减。对于这两种反应类型,牵引力丧失的亚细胞分布既不限于被驱动的微柱附近的位置,也不是在整个细胞中均匀分布,而是沿着细胞周边的离散位置发生。总之,这些数据揭示了外力和内力之间重要的动态生物学关系,并证明了这种微制造系统在探索这种相互作用方面的实用性。