title: Intercellular Transport of Nanomaterials is Mediated by Membrane Nanotubes In Vivo.
abstract: So-called membrane nanotubes are cellular protrusions between cells whose functions include cell communication, environmental sampling, and protein transfer. It has been previously reported that systemically administered carboxyl-modified quantum dots (cQDs) are rapidly taken up by perivascular macrophages in skeletal muscle of healthy mice. Expanding these studies, it is found, by means of in vivo fluorescence microscopy on the mouse cremaster muscle, rapid uptake of cQDs not only by perivascular macrophages but also by tissue-resident cells, which are localized more than 100 μm distant from the closest vessel. Confocal microscopy on muscle tissue, immunostained for the membrane dye DiI, reveals the presence of continuous membranous structures between MHC-II-positive, F4/80-positive cells. These structures contain microtubules, components of the cytoskeleton, which clearly colocalize with cQDs. The cQDs are exclusively found inside endosomal vesicles. Most importantly, by using in vivo fluorescence microscopy, this study detected fast (0.8 μm s(-1) , mean velocity), bidirectional movement of cQDs in such structures, indicating transport of cQD-containing vesicles along microtubule tracks by the action of molecular motors. The findings are the first to demonstrate membrane nanotube function in vivo and they suggest a previously unknown route for the distribution of nanomaterials in tissue.
authors: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Markus
authors: M
authors: Rehberg
authors: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Katharina
authors: K
authors: Nekolla
authors: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Sabine
authors: S
authors: Sellner
authors: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Marc
authors: M
authors: Praetner
authors: MPI for Molecular Biomedicine, Münster, Germany.
authors: Karina
authors: K
authors: Mildner
authors: MPI for Molecular Biomedicine, Münster, Germany.
authors: Dagmar
authors: D
authors: Zeuschner
authors: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors: Fritz
authors: F
authors: Krombach
mesh_terms: D000818:Animals; D001692:Biological Transport; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D043942:Nanotubes
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: bioimaging; in vivo distribution; macrophages; membrane nanotubes; nanoparticles