Pita-Thomas Wolfgang, Steketee Michael B, Moysidis Stavros N, Thakor Kinjal, Hampton Blake, Goldberg Jeffrey L
Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Anatomy and Neurobiology, Washington University, St. Louis, MO, USA.
Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Ophthalmology and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Nanomedicine. 2015 Apr;11(3):559-67. doi: 10.1016/j.nano.2014.11.011. Epub 2015 Jan 14.
Filopodia are 5-10 μm long processes that elongate by actin polymerization, and promote axon growth and guidance by exerting mechanical tension and by molecular signaling. Although axons elongate in response to mechanical tension, the structural and functional effects of tension specifically applied to growth cone filopodia are unknown. Here we developed a strategy to apply tension specifically to retinal ganglion cell (RGC) growth cone filopodia through surface-functionalized, membrane-targeted superparamagnetic iron oxide nanoparticles (SPIONs). When magnetic fields were applied to surface-bound SPIONs, RGC filopodia elongated directionally, contained polymerized actin filaments, and generated retrograde forces, behaving as bona fide filopodia. Data presented here support the premise that mechanical tension induces filopodia growth but counter the hypothesis that filopodial tension directly promotes growth cone advance. Future applications of these approaches may be used to induce sustained forces on multiple filopodia or other subcellular microstructures to study axon growth or cell migration. From the clinical editor: Mechanical tension to the tip of filopodia is known to promote axonal growth. In this article, the authors used superparamagnetic iron oxide nanoparticles (SPIONs) targeted specifically to membrane molecules, then applied external magnetic field to elicit filopodial elongation, which provided a tool to study the role of mechanical forces in filopodia dynamics and function.
丝状伪足是通过肌动蛋白聚合作用而伸长的5-10微米长的突起，通过施加机械张力和分子信号传导来促进轴突生长和导向。尽管轴突会因机械张力而伸长，但专门施加于生长锥丝状伪足的张力的结构和功能影响尚不清楚。在这里，我们开发了一种策略，通过表面功能化、膜靶向的超顺磁性氧化铁纳米颗粒（SPIONs），将张力专门施加于视网膜神经节细胞（RGC）的生长锥丝状伪足上。当对表面结合的SPIONs施加磁场时，RGC丝状伪足会定向伸长，含有聚合的肌动蛋白丝，并产生逆行力，表现为真正的丝状伪足。本文提供的数据支持机械张力诱导丝状伪足生长这一前提，但反驳了丝状伪足张力直接促进生长锥前进这一假说。这些方法未来的应用可能用于对多个丝状伪足或其他亚细胞微结构施加持续力，以研究轴突生长或细胞迁移。临床编辑评论：已知对丝状伪足尖端施加机械张力可促进轴突生长。在本文中，作者使用专门靶向膜分子的超顺磁性氧化铁纳米颗粒（SPIONs），然后施加外部磁场以引发丝状伪足伸长，这为研究机械力在丝状伪足动力学和功能中的作用提供了一种工具。
