Biomedical Microdevices

, Volume 16, Issue 5, pp 717–725 | Cite as

Directed transport of bacteria-based drug delivery vehicles: bacterial chemotaxis dominates particle shape

  • Ali Sahari
  • Mahama A. Traore
  • Birgit E. Scharf
  • Bahareh Behkam


Several attenuated and non-pathogenic bacterial species have been demonstrated to actively target diseased sites and successfully deliver plasmid DNA, proteins and other therapeutic agents into mammalian cells. These disease-targeting bacteria can be employed for targeted delivery of therapeutic and imaging cargos in the form of a bio-hybrid system. The bio-hybrid drug delivery system constructed here is comprised of motile Escherichia coli MG1655 bacteria and elliptical disk-shaped polymeric microparticles. The transport direction for these vehicles can be controlled through biased random walk of the attached bacteria in presence of chemoattractant gradients in a process known as chemotaxis. In this work, we utilize a diffusion-based microfluidic platform to establish steady linear concentration gradients of a chemoattractant and investigate the roles of chemotaxis and geometry in transport of bio-hybrid drug delivery vehicles. Our experimental results demonstrate for the first time that bacterial chemotactic response dominates the effect of body shape in extravascular transport; thus, the non-spherical system could be more favorable for drug delivery applications owing to the known benefits of using non-spherical particles for vascular transport (e.g. relatively long circulation time).


BacteriaBots Drug delivery Bacterial chemotaxis Microfluidics Particle shape 



The authors would like to acknowledge Brian Geuther for helping with the developing of the graphics and Ivan Morozov for the photographs of the device. Our gratitude also goes to our other colleagues in the MicroN BASE laboratory at Virginia Tech especially Meghan A. Canter for helping with particle stretching. This work was in part supported by the National Science Foundation (IIS-117519).

Supplementary material

10544_2014_9876_MOESM1_ESM.docx (409 kb)
ESM 1 (DOCX 409 kb)


  1. G. Adriani, M.D. de Tullio, M. Ferrari, F. Hussain, G. Pascazio, X. Liu, P. Decuzzi, The preferential targeting of the diseased microvasculature by disk-like particles. Biomaterials 33(22), 5504–5513 (2012)CrossRefGoogle Scholar
  2. D. Akin, J. Sturgis, K. Ragheb, D. Sherman, K. Burkholder, J.P. Robinson, A.K. Bhunia, S. Mohammed, R. Bashir, Bacteria-mediated delivery of nanoparticles and cargo into cells. Nat. Nanotechnol. 2, 441–449 (2007)CrossRefGoogle Scholar
  3. C.S. Barker, B.M. Prüß, P. Matsumura, Increased motility of escherichia coli by insertion sequence element integration into the regulatory region of the flhD operon. J. Bacteriol. 186, 7529–7537 (2004)CrossRefGoogle Scholar
  4. B. Behkam, M. Sitti, Bacterial flagella-based propulsion and on/off motion control of microscale objects. Appl. Phys. Lett. 90, 023902–023902–023903 (2007)Google Scholar
  5. H.C. Berg (1993) Random walks in biology: Princeton University Press.Google Scholar
  6. D.A. Canelas, K.P. Herlihy, J.M. DeSimone, Top‐down particle fabrication: control of size and shape for diagnostic imaging and drug delivery. Wiley. Interdiscip. Rev. Nanomed. Nanobiotechnol. 1, 391–404 (2009)CrossRefGoogle Scholar
  7. J.A. Champion, Y.K. Katare, S. Mitragotri, Making polymeric micro-and nanoparticles of complex shapes. Proc. Natl. Acad. Sci. 104, 11901–11904 (2007)CrossRefGoogle Scholar
  8. H.-P. Cheng, G.C. Walker, Succinoglycan is required for initiation and elongation of infection threads during nodulation of alfalfa byRhizobium meliloti. J. Bacteriol. 180, 5183–5191 (1998)Google Scholar
  9. N. Darnton, L. Turner, K. Breuer, H.C. Berg, Moving fluid with bacterial carpets. Biophys. J. 86, 1863–1870 (2004)CrossRefGoogle Scholar
  10. P. Decuzzi, R. Pasqualini, W. Arap, M. Ferrari, Intravascular delivery of particulate systems: does geometry really matter? Pharm. Res. 26, 235–243 (2009)CrossRefGoogle Scholar
  11. M. Ferrari, Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5, 161–171 (2005)CrossRefGoogle Scholar
  12. Y. Geng, P. Dalhaimer, S. Cai, R. Tsai, M. Tewari, T. Minko, D.E. Discher, Shape effects of filaments versus spherical particles in flow and drug delivery. Nat. Nanotechnol. 2, 249–255 (2007)CrossRefGoogle Scholar
  13. S.E. Gratton, P.A. Ropp, P.D. Pohlhaus, J.C. Luft, V.J. Madden, M.E. Napier, J.M. DeSimone, The effect of particle design on cellular internalization pathways. Proc. Natl. Acad. Sci. 105, 11613–11618 (2008)CrossRefGoogle Scholar
  14. R.W. Kasinskas, N.S. Forbes, Salmonella typhimurium lacking ribose chemoreceptors localize in tumor quiescence and induce apoptosis. Cancer Res. 67, 3201–3209 (2007)CrossRefGoogle Scholar
  15. S. Leschner, S. Weiss, Salmonella—allies in the fight against cancer. J. Mol. Med. 88, 763–773 (2010)CrossRefGoogle Scholar
  16. H. Loessner, A. Endmann, S. Leschner, K. Westphal, M. Rohde, T. Miloud, G. Hämmerling, K. Neuhaus, S. Weiss, Remote control of tumour‐targeted Salmonella enterica serovar Typhimurium by the use of l‐arabinose as inducer of bacterial gene expression in vivo. Cell. Microbiol. 9, 1529–1537 (2007)CrossRefGoogle Scholar
  17. H. Mao, P.S. Cremer, M.D. Manson, A sensitive, versatile microfluidic assay for bacterial chemotaxis. Proc. Natl. Acad. Sci. 100, 5449–5454 (2003)CrossRefGoogle Scholar
  18. S. Martel, C.C. Tremblay, S. Ngakeng, G. Langlois, Controlled manipulation and actuation of micro-objects with magnetotactic bacteria. Appl. Phys. Lett. 89, 233904–233904–233903 (2006)Google Scholar
  19. S. Muro, C. Garnacho, J.A. Champion, J. Leferovich, C. Gajewski, E.H. Schuchman, S. Mitragotri, V.R. Muzykantov, Control of endothelial targeting and intracellular delivery of therapeutic enzymes by modulating the size and shape of ICAM-1-targeted carriers. Mol. Ther. 16, 1450–1458 (2008)CrossRefGoogle Scholar
  20. S.J. Park, H. Bae, J. Kim, B. Lim, J. Park, S. Park, Motility enhancement of bacteria actuated microstructures using selective bacteria adhesion. Lab Chip 10, 1706–1711 (2010)CrossRefGoogle Scholar
  21. J.M. Pawelek, K.B. Low, D. Bermudes, Bacteria as tumour-targeting vectors. The Lancet Oncology 4, 548–556 (2003)CrossRefGoogle Scholar
  22. D. Peer, J.M. Karp, S. Hong, O.C. Farokhzad, R. Margalit, R. Langer, Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2, 751–760 (2007)CrossRefGoogle Scholar
  23. A. Sahari, D. Headen, B. Behkam, Effect of body shape on the motile behavior of bacteria-powered swimming microrobots (BacteriaBots). Biomed. Microdevices 14, 999–1007 (2012)CrossRefGoogle Scholar
  24. J. Sambrook, E.F. Fritsch, T. Maniatis, Molecular cloning, Cold Spring Harbor Laboratory Press, New York, 1989Google Scholar
  25. J.E. Segall, S.M. Block, H.C. Berg, Temporal comparisons in bacterial chemotaxis. Proc. Natl. Acad. Sci. 83, 8987–8991 (1986)CrossRefGoogle Scholar
  26. M.S. Springer, M.F. Goy, J. Adler, Sensory transduction in escherichia coli: two complementary pathways of information processing that involve methylated proteins. Proc. Natl. Acad. Sci. 74, 3312–3316 (1977)CrossRefGoogle Scholar
  27. E. Steager, C.-B. Kim, J. Patel, S. Bith, C. Naik, V. Reber, M.J. Kim, Control of microfabricated structures powered by flagellated bacteria using phototaxis. Appl. Phys. Lett. 90, 263901–263901–263903 (2007)Google Scholar
  28. J. Stritzker, S. Weibel, P.J. Hill, T.A. Oelschlaeger, W. Goebel, A.A. Szalay, Tumor-specific colonization, tissue distribution, and gene induction by probiotic Escherichia coli nissle 1917 in live mice. Int. J. Med. Microbiol. 297, 151–162 (2007)CrossRefGoogle Scholar
  29. L. Tao, W. Hu, Y. Liu, G. Huang, B.D. Sumer, J. Gao, Shape-specific polymeric nanomedicine: emerging opportunities and challenges. Exp. Biol. Med. 236, 20–29 (2011)CrossRefGoogle Scholar
  30. M.A. Traore, B. Behkam, A PEG-DA microfluidic device for chemotaxis studies. J. Micromech. Microeng. 23, 085014 (2013)CrossRefGoogle Scholar
  31. M.A. Traoré, A. Sahari, B. Behkam, Computational and experimental study of chemotaxis of an ensemble of bacteria attached to a microbead. Phys. Rev. E. 84, 061908 (2011)CrossRefGoogle Scholar
  32. P.C. Weber, D. Ohlendorf, J. Wendoloski, F. Salemme, Structural origins of high-affinity biotin binding to streptavidin. Science 243, 85–88 (1989)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ali Sahari
    • 1
  • Mahama A. Traore
    • 2
  • Birgit E. Scharf
    • 3
  • Bahareh Behkam
    • 1
    • 2
  1. 1.School of Biomedical Engineering and SciencesVirginia Tech–Wake Forest UniversityBlacksburgUSA
  2. 2.Department of Mechanical EngineeringVirginia TechBlacksburgUSA
  3. 3.Department of Biological SciencesVirginia TechBlacksburgUSA

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