title: Promoting filopodial elongation in neurons by membrane-bound magnetic nanoparticles.
abstract: 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.
authors.affiliation: 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.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pita-Thomas
authors.affiliation: 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.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Steketee
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Stavros N
authors.initials: SN
authors.lastname: Moysidis
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Kinjal
authors.initials: K
authors.lastname: Thakor
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Blake
authors.initials: B
authors.lastname: Hampton
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Ophthalmology, Shiley Eye Center, UC San Diego, San Diego, CA, USA. Electronic address: JLGoldberg@ucsd.edu.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020439:Growth Cones / Q000378:metabolism*; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D011554:Pseudopodia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D058185:Magnetite Nanoparticles
keywords: Axon growth; Filopodia; Mechanical tension; Nanoparticles