title: Nanodiamond-Mediated Intercellular Transport of Proteins through Membrane Tunneling Nanotubes.
abstract: Recently discovered tunneling nanotubes (TNTs) are capable of creating intercellular communication pathways through which transport of proteins and other cytoplasmic components occurs. Intercellular transport is related to many diseases and nanotubes are potentially useful as drug-delivery channels for cancer therapy. Here, we apply fluorescent nanodiamond (FND) as a photostable tracker, as well as a protein carrier, to illustrate the transport events in TNTs of human cells. Proteins, including bovine serum albumin and green fluorescent protein, are first coated on 100-nm FNDs by physical adsorption and then single-particle tracking of the bioconjugates in the transient membrane connections is carried out by fluorescence microscopy. Stop-and-go and to-and-fro motions mediated by molecular motors are found for the active transport of protein-loaded FNDs trapped in the endosomal vehicles of human embryonic kidney cells (HEK293T). Quantitative analysis of the heterotypical transport between HEK293T and SH-SY5Y neuroblastoma cells by flow cytometry confirm the formation of open-ended nanotubes between them, despite that their TNTs differ in structural components. Our results demonstrate the promising applications of this novel carbon-based nanomaterial for intercellular delivery of biomolecular cargo down to the single-particle level.
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan.|Taiwan International Graduate Program - Molecular Science and Technology, Academia Sinica, Taipei, 115, Taiwan.|Department of Chemistry, National Tsing Hua University, Hsinchu, 300, Taiwan.
authors.forename: Chandra Prakash
authors.initials: CP
authors.lastname: Epperla
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan.
authors.forename: Nitin
authors.initials: N
authors.lastname: Mohan
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan.|Department of Chemistry, National Taiwan Normal University, Taipei, 116, Taiwan.
authors.forename: Che-Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan.|Department of Chemistry, National Taiwan Normal University, Taipei, 116, Taiwan.
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan.|Taiwan International Graduate Program - Molecular Science and Technology, Academia Sinica, Taipei, 115, Taiwan.|Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, 106, Taiwan.
authors.forename: Huan-Cheng
authors.initials: HC
authors.lastname: Chang
mesh_terms: D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D000067493:Dynamic Light Scattering; D004591:Electrophoresis, Polyacrylamide Gel; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D058612:Nanodiamonds / Q000737:chemistry*; D043942:Nanotubes / Q000737:chemistry*; D011506:Proteins / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013997:Time Factors
chemical_list: D058612:Nanodiamonds; D011506:Proteins; D049452:Green Fluorescent Proteins; D012710:Serum Albumin, Bovine
keywords: intercellular transport; nanoparticles; nanotubes; nanovesicles, nanodiamonds; proteins