JBNB  Vol.2 No.2 , April 2011
Microscopic observation of the intercellular transport of CdTe quantum dot aggregates through tunneling-nanotubes
Abstract: Various inorganic nanoparticles are being considered for applications in life science as fluorescent labels and for such therapeutic applications as drug delivery or targeted cell destruction. It is of importance to understand their intercellular transport behaviors and mechanisms. Here, the intercellular transport of internalized CdTe quantum dot (QD) aggregates through tunneling-nanotubes (TNTs) between human hepatocellular carcinoma cells was studied by time-resolved confocal fluorescence microscopy. TNTs are known to connect eukaryotic cells to provide important pathways for intercellular communications. The formation, shrinkage, elongation and rupture of TNTs were clearly observed by microscopy. We found TNTs contained only F-actin or both microtubules and F-actin. Two transport modes for QD aggregates through the TNTs were observed: the microtubule-based bidirectional motion and the ac-tin-dependent unidirectional motion. The mean square displacement analyses revealed that the intercellular transportations of QDs along TNTs were mediated by active processes. The bidirectional intercellular transport of QDs within lysosomes through the TNT was also observed.
Cite this paper: nullL. Mi, R. Xiong, Y. Zhang, W. Yang, J. Chen and P. Wang, "Microscopic observation of the intercellular transport of CdTe quantum dot aggregates through tunneling-nanotubes," Journal of Biomaterials and Nanobiotechnology, Vol. 2 No. 2, 2011, pp. 172-179. doi: 10.4236/jbnb.2011.22022.

[1]   [1] A. Rustom, R. Saffrich, I. Markovic, P. Walther and H. H. Gerdes, “Notubular Highways for Intercellular Organelle Transport,” Science, Vol. 303, No. 5660, 2004, pp. 1007- 1010. doi:10.1126/science.1093133

[2]   [2] H. R. Chinnery, E. Pearlman and P. G. McMenamin, “Cutting Edge: Membrane Nanotubes in Vivo: A Feature of Mhc Class Ii+ Cells in The Mouse Corneal,” The Journal of Immunology, Vol. 180, No. 9, 2008, pp. 5779-5783.

[3]   [3] K. Gousset, E. Schiff, C. Langevin, Z. Marijanovic, A. Caputo, D. T. Browman, N. Chenouard, F. de Chaumont, A. Martino, J. Enninga, J. C. Olivo-Marin, D. Mannel and C. Zurzolo, “Prions Hijack Tunnelling Nanotubes for In-tercellular Spread,” Nature Cell Biology, Vol. 11, No. 3, 2009, pp. 328-336. doi:10.1038/ncb1841

[4]   [4] D. M. Davis and S. Sowinski, “Membrane Nanotubes: Dynamic Long-Distance Connections between Animal Cells,” Nature Reviews Molecular Cell Biology, Vol. 9, No. 6, 2008, pp. 431-436. doi:10.1038/nrm2399

[5]   [5] S. C. Watkins and R. D. Salter, “Functional Connectivity between Immune Cells Mediated by Tunneling Nano-tubules,” Immunity, Vol. 23, No. 2005, pp. 309-318.

[6]   [6] B. Onfelt, S. Nedvetzki, K. Yanagi and D. M. Davis, “Cutting Edge: Membrane Nanotubes Connect Immune Cells,” Journal of Immunology, Vol. 173, No. 3, 2004, pp. 1511-1513.

[7]   [7] B. Onfelt, S. Nedvetzki, R. K. P. Benninger, M. A. Purb-hoo, S. Sowinski, A. N. Hume, M. C. Seabra, M. A. A. Neil, P. M. W. French and D. M. Davis, “Structurally Distinct Membrane Nanotubes between Human Macro-phages Support Long-Distance Vesicular Traffic or Surf-ing of Bacteria,” Journal of Immunology, Vol. 177, No. 12, 2006, pp. 8476-8483.

[8]   [8] S. Sowinski, C. Jolly, O. Berninghausen, M. A. Purbhoo, A. Chauveau, K. Kohler, and et al. , “Membrane nano-tubes Physically Connect T Cells over Long Distances Presenting a Novel Route for Hiv-1 Transmission,” Na-ture Cell Biology, Vol. 10, No. 2, 2008, pp. 211-219. doi:10.1038/ncb1682

[9]   [9] O. Rechavi, I. Goldstein and Y. Kloog, “Intercellular Exchange of Proteins: The Immune Cell Habit of Shar-ing,” FEBS Letters, Vol. 583, No. 11, 2009, pp. 1792- 1799. doi:10.1016/j.febslet.2009.03.014

[10]   [10] D. M. Davis, “Mechanisms and Functions for the Dura-tion of Intercellular Contacts Made by Lymphocytes,” Nature Reviews Immunology, Vol. 9, No. 8, 2009, pp. 543-555. doi:10.1038/nri2602

[11]   [11] E. A. Eugenin, P. J. Gaskill and J. W. Berman, “Tunnel-ing Nanotubes (Tnt) are Induced by Hiv-Infection of Macrophages: A Potential Mechanism for Intercellular Hiv Trafficking,” Cell Immunology, Vol. 254, No. 2, 2009, pp. 142-148. doi:10.1016/j.cellimm.2008.08.005

[12]   [12] P. Veranic, M. Lokar, G. J. Schutz, J. Weghuber, S. Wie-ser, H. Haegerstrand, V. Kralj-Iglic and A. Iglic, “Differ-ent Types of Cell-to-Cell Connections Mediated by Nano- tubular Structures,” Biophysical Journal, Vol. 95, No. 9, 2008, pp. 4416-4425. doi:10.1529/biophysj.108.131375

[13]   [13] S. Gurke, J. F. V. Barroso, E. Hodneland, N. V. Buko-reshtliev, O. Schlicker and H. H. Gerdes, “Tunneling Nanotube (Tnt)-Like Structures Facilitate a Constitutive, Actomyosin-Dependent Exchange of Endocytic Organ-elles between Normal Rat Kidney Cells,” Experimental Cell Research, Vol. 314, No. 20, 2008, pp. 3669-3683. doi:10.1016/j.yexcr.2008.08.022

[14]   [14] N. M. Sherer, M. J. Lehmann, L. F. Jimenez-Soto, C. Horensavitz, M. Pypaert and W. Mothes, “Retroviruses Can Establish Filopodial Bridges for Efficient Cell-To- Cell Transmission,” Nature Cell Biology, Vol. 9, No. 3, 2007, pp. 310-315. doi:10.1038/ncb1544

[15]   [15] M. Lokar, A. Igli? and P. Verani?, “Protruding Membrane Nanotubes: Attachment of Tubular Protrusions to Adja-cent Cells by Several Anchoring Junctions,” Protoplasma, Vol. 246, 2010, pp. 81-87. doi:10.1007/s00709-010-0143-7

[16]   [16] F. B. Nimita H. Fifadara, Shoichiro Ono and Santa J. Ono, “Interaction between Activated Chemokine Receptor 1 and Fceri at Membrane Rafts Promotes Communication and F-Actin-Rich Cytoneme Extensions between Mast Cells,” International Immunology, Vol. 22, No. 2, 2010, pp. 113-128. doi:10.1093/intimm/dxp118

[17]   [17] P. Tavi, T. Korhonen, S. L. H. Nninen, J. D. Bruton, S. L??f, A. Simon and H. Westerblad, “Myogenic Skeletal Muscle Satellite Cells Communicate by Tunnelling Na-notubes,” Journal of Cellular Physiology, Vol. 223, No. 2, 2010, pp. 376-383.

[18]   [18] M. Koyanagi, R. P. Brandes, J. Haendeler, A. M. Zeiher and S. Dimmeler, “Cell-to-Cell Connection of Endothe-lial Progenitor Cells With Cardiac Myocytes by Nano-tubes,” Circulation Research, Vol. 96, 2005, pp. 1039- 1041. doi:10.1161/01.RES.0000168650.23479.0c

[19]   [19] K. He, W. Luo, Y. Zhang, F. Liu, D. Liu, L. Xu, L. Qin, C. Xiong, Z. Lu, X. Fang and Y. Zhang, “Intercellular Transfer of Quantum Dots Mediated by Membrane Na-notubes,” ACS Nano, Vol. 4, No. 6, 2010, pp. 3015-3022. doi:10.1021/nn1002198

[20]   [20] B. Fadeel and A. E. Garcia-Bennett, “Better safe than sorry: Understanding the Toxicological Properties of In-organic Nanoparticles Manufactured for Biomedical Ap-plications,” Advanced Drug Delivery Reviews, Vol. 62, No. 3, 2010, pp. 362-374. doi:10.1016/j.addr.2009.11.008

[21]   [21] M. Liong, J. Lu, M. Kovochich, T. Xia, S. G. Ruehm, A. E. Nel, F. Tamanoi and J. I. Zink, “Multifunctional Inor-ganic Nanoparticles for Imaging, Targeting, and Drug Delivery,” ACS Nano, Vol. 2, No. 5, 2008, pp. 889-896. doi:10.1021/nn800072t

[22]   [22] J. Rao, A. Dragulescu-Andrasi and H. Yao, “Fluorescence Imaging in Vivo: Recent Advances,” Current Opinion in Cell Biology, Vol. 18, 2007, pp. 17-25.

[23]   [23] J. Gao and B. Xu, “Applications of nanomaterials inside cells,” Nano Today, Vol. 4, 2009, pp. 37-51. doi:10.1016/j.nantod.2008.10.009

[24]   [24] J. Guo, W. L. Yang and C. C. Wang, “Systematic Study of the Photoluminescence Dependence of Thiol-Capped CdTe Nanocrystals on the Reaction Conditions,” Journal Of Physical Chemistry, Vol. 109, 2005, pp. 17467-17473. doi:10.1021/jp044770z

[25]   [25] H. H. Gerdes, N. V. Bukoreshtliev and J. F. V. Barroso, “Tunneling nanotubes: A New Route for the Exchange of Components between Animal Cells,” FEBS Letter, Vol. 581, No. 11, 2007, pp. 2194-2201. doi:10.1016/j.febslet.2007.03.071

[26]   [26] S. Gurke, J. F. V. Barroso and H. H. Gerdes, “The Art of Cellular Communication: Tunneling Nanotubes Bridge the Divide,” Histochemistry and Cell Biology, Vol. 129, No. 5, 2008, pp. 539-550. doi:10.1007/s00418-008-0412-0

[27]   [27] D. Raucher and M. P. Sheetz, “Characteristics of a Mem-brane Reservoir Buffering Membrane Tension,” Bio-physical Journal, Vol. 77, 1999, pp. 1992-2002. doi:10.1016/S0006-3495(99)77040-2

[28]   [28] M. Sun, J. S. Graham, B. Hegedüs, F. Marga, Y. Zhang, G. Forgacs and M. Grandbois, “Multiple Membrane Tethers Probed by Atomic Force Microscopy,” Biophysi-cal Journal , Vol. 89, 2005, pp. 4320-4329.

[29]   doi:10.1529/biophysj.104.058180 [29] G. Ruan, A. Agrawal, A. I. Marcus and S. Nie, “Imaging and Tracking of Tat Peptide-Conjugated Quantum Dots in Living Cells: New Insights into Nanoparticle Uptake, In-tracellular Transport, and Vesicle Shedding,” Journal of the American Chemical Society, Vol. 129, 2007, pp. 14759-14766. doi:10.1021/ja074936k

[30]   [30] A. M. Smith, H. Duan, A. M. Mohs and S. Nie, “Biocon-jugated Quantum Dots for in Vivo Molecular and Cellular Imaging,” Advanced Drug Delivery Reviews, Vol. 60, 2008, pp. 1226-1240. doi:10.1016/j.addr.2008.03.015

[31]   [31] M. J. Saxton, “Anomalous Diffusion Due to Obstacles: A Monte Carlo Study,” Biophysical Journal, Vol. 66, 1994, pp. 394-401. doi:10.1016/S0006-3495(94)80789-1

[32]   [32] M. Lokar, ?. Perutková, V. Kralj-Igli?, A. Igli? and P. Verani?, “Advances in Planar Lipid Bilayers and Lipo-somes,” Elsevier: Burlington, 2009; Vol. 10. doi:10.1016/S1554-4516(09)10003-0

[33]   [33] A. Igli?, M. Lokar, B. Babnik, T. Slivnik and P. Verani?, “Possible Role of Flexible Red Blood Cell Membrane Nanodomains in the Growth and Stability of Membrane Nanotubes,” Blood Cells Molecules, and Diseases, Vol. 39, 2007, pp. 14-23. doi:10.1016/j.bcmd.2007.02.013

[34]   [34] S. P. Gross, “Hither and Yon: A Review of Bi-Directional Microtubule-Based Transport,” Physical Biology, Vol. 1, 2004, pp. R1-R11. doi:10.1088/1478-3967/1/2/R01

[35]   [35] Y. Zhang, L. Mi, R. Xiong, P.-N. Wang, J.-Y. Chen, W. Yang, C. Wang and Q. Peng, “Subcellular Localization of Thiol-Capped CdTe Quantum Dots in Living Cells,” Na Nanoscale Research Letters, Vol. 4, 2009, pp. 606-612. doi:10.1007/s11671-009-9307-9