Intercellular Transport of Nanomaterials is Mediated by Membrane Nanotubes In Vivo. Issue 14 (8th February 2016)

• Record Type: Journal Article
• Authors: Rehberg, Markus; Nekolla, Katharina; Sellner, Sabine; Praetner, Marc; Mildner, Karina; Zeuschner, Dagmar; Krombach, Fritz
• Is Part Of: Small. Volume 12:Issue 14(2016)
• Page Start: 1882
• Page End: 1890
• Publication Date: 2016-02-08
• Subjects: bioimaging -- in vivo distribution -- macrophages -- membrane nanotubes -- nanoparticles; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201503606
• Languages: English
• ISSNs: 1613-6810

Abstract

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. Abstract : Cellular uptake of (nano)materials from the bloodstream and their subsequent distribution in tissue is a crucial step for diverse drug delivery approaches. This study describes the presence of microtubule‐containing membrane nanotubes connecting perivascular and tissue‐resident macrophages in skeletal muscle tissue. Perivascular macrophages are able to sample nanoparticles from the blood stream, which are then actively transported in the muscle within membrane nanotubes.