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Mechanoporation: Toward Single Cell Approaches

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Handbook of Single Cell Technologies

Abstract

A cell is an independent functioning unit, and it regulates its input and output based on its own genetic makeup omitting any external transcriptions. Unlike bulk measurement with millions of cells together, which provides an average data, single-cell analysis (SCA) can reflect physiological information of each individual cell and therefore is essential to understand cellular characteristics precisely. For SCA, the delivery of certain molecules into a specific cell type is a challenging task, and it is essential to come up with novel methods to achieve such a goal. Mechanoporation is an emerging and promising method for single-cell intracellular delivery, where mechanical energy is used to create transient hydrophilic membrane pores to deliver cargo into the target cell with high transfection efficiency and high cell viability. This method does not depend on the type of cell to be delivered. In this chapter, we have briefly discussed different single-cell mechanoporation devices based on the source of mechanical forces used to create transient membrane pores and intracellular delivery. In addition, the advantages and limitations of each technique are compared, and future prospects are highlighted.

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References

  • Adamo A, Jensen KF (2008) Microfluidic based single cell microinjection. Lab Chip 8:1258–1261

    Article  Google Scholar 

  • Adamo A, Roushdy O, Dokov R, Sharei A, Jensen KF (2013) Microfluidic jet injection for delivering macromolecules into cells. J Micromechanics Microengineering 23:35026

    Article  Google Scholar 

  • Barber MA (1911) A technic for the inoculation of bacteria and other substances into living cells. J Infect Dis 8:348–360

    Article  Google Scholar 

  • Castiglioni P, Gerloni M, Zanetti M (2004) Genetically programmed B lymphocytes are highly efficient in inducing anti-virus protective immunity mediated by central memory CD8 T cells. Vaccine 23:699–708

    Article  Google Scholar 

  • Cho HJ, Takabayashi K, Cheng P-M, Nguyen M-D, Corr M, Tuck S, Raz E (2000) Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism. Nat Biotechnol 18:509

    Article  Google Scholar 

  • Colosimo A, Goncz KK, Holmes AR, Kunzelmann K, Novelli G, Malone RW, Bennett MJ, Gruenert DC (2000) Transfer and expression of foreign genes in mammalian cells. BioTechniques 29:314–331

    Article  Google Scholar 

  • Cross D, Burmester JK (2006) Gene therapy for Cancer treatment: past, present and future. Clin Med Res 4:218–227. https://doi.org/10.3121/cmr.4.3.218

    Article  Google Scholar 

  • Cuerrier CM, Lebel R, Grandbois M (2007) Single cell transfection using plasmid decorated AFM probes. Biochem Biophys Res Commun 355:632–636

    Article  Google Scholar 

  • Davis SP, Martanto W, Allen MG, Prausnitz MR (2005) Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans Biomed Eng 52:909–915

    Article  Google Scholar 

  • Dijkmans PA, Juffermans LJM, Musters RJP, van Wamel A, Ten Cate FJ, van Gilst W, Visser CA, de Jong N, Kamp O (2004) Microbubbles and ultrasound: from diagnosis to therapy. Eur J Echocardiogr 5:245–246

    Article  Google Scholar 

  • Ding X, Stewart MP, Sharei A, Weaver JC, Langer RS, Jensen KF (2017) High-throughput nuclear delivery and rapid expression of DNA via mechanical and electrical cell-membrane disruption. Nat Biomed Eng 1:39

    Article  Google Scholar 

  • Dixon AJ, Dhanaliwala AH, Chen JL, Hossack JA (2013) Enhanced intracellular delivery of a model drug using microbubbles produced by a microfluidic device. Ultrasound Med Biol 39:1267–1276

    Article  Google Scholar 

  • Dong C, Lei XX (2000) Biomechanics of cell rolling: shear flow, cell-surface adhesion, and cell deformability. J Biomech 33:35–43

    Article  Google Scholar 

  • Du S, Li Y (2007) Micromanipulation based on AFM: probe tip selection. In: Nanotechnology, 2007. IEEE-NANO 2007. 7th IEEE Conference on. pp 506–510

    Google Scholar 

  • Fox Robert W, McDonald Alan T, Pritchard Philip J (2004) Introduction to fluid mechanics. Wiley, Hoboken

    MATH  Google Scholar 

  • Gerdes H-H, Kaether C (1996) Green fluorescent protein: applications in cell biology. FEBS Lett 389:44–47. https://doi.org/10.1016/0014-5793(96)00586-8

    Article  Google Scholar 

  • Hallow DM, Seeger RA, Kamaev PP, Prado GR, LaPlaca MC, Prausnitz MR (2008) Shear-induced intracellular loading of cells with molecules by controlled microfluidics. Biotechnol Bioeng 99:846–854

    Article  Google Scholar 

  • Han X, Liu Z, Jo MC, Zhang K, Li Y, Zeng Z, Li N, Zu Y, Qin L (2015) CRISPR-Cas9 delivery to hard-to-transfect cells via membrane deformation. Sci Adv 1:e1500454. https://doi.org/10.1126/sciadv.1500454

    Article  Google Scholar 

  • Ikuo O, Chikashi N, Han S, Nakamura N, Miyake J (2004) Nanoscale operation of a living cell using an atomic force microscope with a Nanoneedle. Nano Lett. https://doi.org/10.1021/NL0485399

    Article  Google Scholar 

  • Ivanov IT (1999) Spectrofluorometric and microcalorimetric study of the thermal poration relevant to the mechanism of thermohaemolysis. Int J Hyperth 15:29–43

    Article  Google Scholar 

  • Juliano RL, Alam R, Dixit V, Kang HM (2009) Cell-targeting and cell-penetrating peptides for delivery of therapeutic and imaging agents. Wiley Interdiscip Rev Nanomedicine Nanobiotechnology 1:324–335

    Article  Google Scholar 

  • Knight AM (2015) B-cell acquisition of antigen: sensing the surface. Eur J Immunol 45:1600–1604

    Article  Google Scholar 

  • Kotopoulis S, Eder SD, Greve MM, Holst B, Postema M (2013) Lab-on-a-chip device for fabrication of therapeutic microbubbles on demand. Biomed Tech 58 (Suppl. 1), https://doi.org/10.1515/bmt-2013–4037

  • Kristensen M, Birch D, Mørck Nielsen H (2016) Applications and challenges for use of cell-penetrating peptides as delivery vectors for peptide and protein cargos. Int J Mol Sci 17:185

    Article  Google Scholar 

  • Lakshmanan S, Gupta GK, Avci P, Chandran R, Sadasivam M, Jorge AES, Hamblin MR (2014) Physical energy for drug delivery; poration, concentration and activation. Adv Drug Deliv Rev 71:98–114. https://doi.org/10.1016/j.addr.2013.05.010

    Article  Google Scholar 

  • Lanzavecchia A (1985) Antigen-specific interaction between T and B cells. Nature 314:537

    Article  Google Scholar 

  • Lee Szeto G, Van Egeren D, Worku H, Sharei A, Alejandro B, Park C, Frew K, Brefo M, Mao S, Heimann M, Langer R, Jensen KF, Irvine DJ (2015) Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines. Sci Rep 5:10276. https://doi.org/10.1038/srep10276

    Article  Google Scholar 

  • Lee S, Jeong W, Beebe DJ (2003) Microfluidic valve with cored glass microneedle for microinjection. Lab Chip 3:164–167

    Article  Google Scholar 

  • Li ZG, Liu AQ, Klaseboer E, Zhang JB, Ohl CD (2013) Single cell membrane poration by bubble-induced microjets in a microfluidic chip. Lab Chip 13:1144–1150

    Article  Google Scholar 

  • Ludtke JJ, Sebestyén MG, Wolff JA (2002) The effect of cell division on the cellular dynamics of microinjected DNA and dextran. Mol Ther 5:579–588

    Article  Google Scholar 

  • Madani F, Lindberg S, Langel Ãœ, Futaki S, Gräslund A (2011) Mechanisms of cellular uptake of cell-penetrating peptides. J Biophys 2011:1–10

    Article  Google Scholar 

  • Matsumoto D, Sathuluri RR, Kato Y, Silberberg YR, Kawamura R, Iwata F, Kobayashi T, Nakamura C (2015) Oscillating high-aspect-ratio monolithic silicon nanoneedle array enables efficient delivery of functional bio-macromolecules into living cells. Sci Rep 5:15325

    Article  Google Scholar 

  • Matsumoto D, Yamagishi A, Saito M, Sathuluri RR, Silberberg YR, Iwata F, Kobayashi T, Nakamura C (2016) Mechanoporation of living cells for delivery of macromolecules using nanoneedle array. J Biosci Bioeng 122:748–752. https://doi.org/10.1016/j.jbiosc.2016.05.006

    Article  Google Scholar 

  • Matthews K, Myrand-Lapierre M-E, Ang RR, Duffy SP, Scott MD, Ma H (2015) Microfluidic deformability analysis of the red cell storage lesion. J Biomech 48:4065–4072

    Article  Google Scholar 

  • McNeil PL, Khakee R (1992) Disruptions of muscle fiber plasma membranes. Role in exercise-induced damage. Am J Pathol 140:1097

    Google Scholar 

  • Meister A, Gabi M, Behr P, Studer P, Vörös J, Niedermann P, Bitterli J, Polesel-Maris J, Liley M, Heinzelmann H et al (2009) FluidFM: combining atomic force microscopy and nanofluidics in a universal liquid delivery system for single cell applications and beyond. Nano Lett 9:2501–2507

    Article  Google Scholar 

  • Milletti F (2012) Cell-penetrating peptides: classes, origin, and current landscape. Drug Discov Today 17:850–860

    Article  Google Scholar 

  • Nair-Gupta P, Baccarini A, Tung N, Seyffer F, Florey O, Huang Y, Banerjee M, Overholtzer M, Roche PA, Tampé R et al (2014) TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation. Cell 158:506–521

    Article  Google Scholar 

  • Nakamura C, Kamiishi H, Nakamura N, Miyake J (2008) A nanoneedle can be inserted into a living cell without any mechanical stress inducing calcium ion influx. Electrochemistry 76:586–589. https://doi.org/10.5796/electrochemistry.76.586

    Article  Google Scholar 

  • Newman CMH, Bettinger T (2007) Gene therapy progress and prospects: ultrasound for gene transfer. Gene Ther 14:465

    Article  Google Scholar 

  • Noori A, Selvaganapathy PR, Wilson J (2009) Microinjection in a microfluidic format using flexible and compliant channels and electroosmotic dosage control. Lab Chip 9:3202–3211

    Article  Google Scholar 

  • Pack DW, Hoffman AS, Pun S, Stayton PS (2005) Design and development of polymers for gene delivery. Nat Rev Drug Discov 4:581

    Article  Google Scholar 

  • Pak OS, Young Y-N, Marple GR, Veerapaneni S, Stone HA (2015) Gating of a mechanosensitive channel due to cellular flows. Proc Natl Acad Sci 112:9822–9827. https://doi.org/10.1073/pnas.1512152112

    Article  Google Scholar 

  • Palumbo G, Caruso M, Crescenzi E, Tecce MF, Roberti G, Colasanti A (1996) Targeted gene transfer in eucaryotic cells by dye-assisted laser optoporation. J Photochem Photobiol B Biol 36:41–46

    Article  Google Scholar 

  • Park H, Lee S, Ji M, Kim K, Son Y, Jang S, Park Y (2016) Measuring cell surface area and deformability of individual human red blood cells over blood storage using quantitative phase imaging. Sci Rep 6:34257

    Article  Google Scholar 

  • Peer E, Artzy-Schnirman A, Gepstein L, Sivan U (2012) Hollow nanoneedle array and its utilization for repeated administration of biomolecules to the same cells. ACS Nano 6:4940–4946

    Article  Google Scholar 

  • Plank C, Zelphati O, Mykhaylyk O (2011) Magnetically enhanced nucleic acid delivery. Ten years of magnetofection-Progress and prospects. Adv Drug Deliv Rev 63:1300–1331

    Article  Google Scholar 

  • Ratledge C, Kristiansen B (2006) Basic biotechnology. Cambridge University Press, Cambridge, UK

    Book  Google Scholar 

  • Sanford JC, Klein TM, Wolf ED, Allen N (1987) Delivery of substances into cells and tissues using a particle bombardment process. Part Sci Technol 5:27–37

    Article  Google Scholar 

  • Santra TS, Tseng FG (2013) Recent trends on micro/nanofluidic single cell electroporation. Micromachines 4:333–356. https://doi.org/10.3390/mi4030333

    Article  Google Scholar 

  • Santra TS, Tseng FG (2014) Micro/nanofluidic devices for single cell analysis. Micromachines 5(2):154–157

    Article  Google Scholar 

  • Santra TS, Chen C-W, Chang H-Y, Tseng F-G (2016) Dielectric passivation layer as a substratum on localized single-cell electroporation. RSC Adv 6:10979–10986

    Article  Google Scholar 

  • Santra TS, Michael A, Teitell, Pei-yu E, Chiou (2018) Device for massively parallel high throughput single cell electroporation and uses thereof. U.S. Patent Application 15(673):255

    Google Scholar 

  • Shanmugam MM, Santra TS (2016) Microinjection for single-cell analysis. Springer, Berlin/Heidelberg, pp 85–129

    Google Scholar 

  • Sharei A, Zoldan J, Adamo A, Sim WY, Cho N, Jackson E, Mao S, Schneider S, Han M-J, Lytton-Jean A, Basto PA, Jhunjhunwala S, Lee J, Heller DA, Kang JW, Hartoularos GC, Kim K-S, Anderson DG, Langer R, Jensen KF (2013) A vector-free microfluidic platform for intracellular delivery. Proc Natl Acad Sci 110:2082–2087. https://doi.org/10.1073/pnas.1218705110

    Article  Google Scholar 

  • Sharei A, Poceviciute R, Jackson EL, Cho N, Mao S, Hartoularos GC, Jang DY, Jhunjhunwala S, Eyerman A, Schoettle T et al (2014) Plasma membrane recovery kinetics of a microfluidic intracellular delivery platform. Integr Biol 6:470–475

    Article  Google Scholar 

  • Silberberg YR, Mieda S, Amemiya Y, Sato T, Kihara T, Nakamura N, Fukazawa K, Ishihara K, Miyake J, Nakamura C (2013) Evaluation of the actin cytoskeleton state using an antibody-functionalized nanoneedle and an AFM. Biosens Bioelectron 40:3–9. https://doi.org/10.1016/j.bios.2012.06.044

    Article  Google Scholar 

  • Sohn RL, Murray MT, Schwarz K, Nyitray J, Purray P, Franko AP, Palmer KC, Diebel LN, Dulchavsky SA (2001) In-vivo particle mediated delivery of mRNA to mammalian tissues: ballistic and biologic effects. Wound Repair Regen 9:287–296

    Article  Google Scholar 

  • Sokol E, Nijenhuis M, Sjollema KA, Jonkman MF, Pas HH, Giepmans BNG (2017) Particle bombardment of ex vivo skin to deliver DNA and express proteins. In: Inflammation. Springer, Humana Press, New York, NY, pp 107–118

    Google Scholar 

  • Stride E, Saffari N (2003) Microbubble ultrasound contrast agents: a review. Proc Inst Mech Eng Part H J Eng Med 217:429–447

    Article  Google Scholar 

  • Tseng FG, Santra TS (2016) Essentials of single-cell analysis. Springer-Verlag: Berlin/Heidelberg, Germany

    Google Scholar 

  • Tuhin FT, Santra S. Prospects F Essentials of Single-Cell Analysis

    Google Scholar 

  • Uchida M, Li XW, Mertens P, Alpar HO (2009) Transfection by particle bombardment: delivery of plasmid DNA into mammalian cells using gene gun. Biochim Biophys Acta (BBA)-General Subj 1790:754–764

    Article  Google Scholar 

  • Valero A, Merino F, Wolbers F, Luttge R, Vermes I, Andersson H, van den Berg A (2005) Apoptotic cell death dynamics of HL60 cells studied using a microfluidic cell trap device. Lab Chip 5:49–55

    Article  Google Scholar 

  • Waehler R, Russell SJ, Curiel DT (2007) Engineering targeted viral vectors for gene therapy. Nat Rev Genet 8:573

    Article  Google Scholar 

  • Xu Q (2018) Review of microinjection systems. In: Micromachines for biological micromanipulation. Springer, Cham, pp 15–47

    Chapter  Google Scholar 

  • Yang H, Xiong X, Zhang L, Wu C, Liu Y (2011) Adhesion of bio-functionalized ultrasound microbubbles to endothelial cells by targeting to vascular cell adhesion molecule-1 under shear flow. Int J Nanomedicine 6:2043

    Google Scholar 

  • Zabner J (1997) Cationic lipids used in gene transfer. Adv Drug Deliv Rev 27:17–28

    Article  Google Scholar 

  • Zelenin AV, Kolesnikov VA, Tarasenko OA, Shafei RA, Zelenina IA, Mikhailov VV, Semenova ML, Kovalenko DV, Artemyeva OV, Ivaschenko TE et al (1997) Bacterial $β$-galactosidase and human dystrophin genes are expressed in mouse skeletal muscle fibers after ballistic transfection. FEBS Lett 414:319–322

    Article  Google Scholar 

  • Zhang X, Godbey WT (2006) Viral vectors for gene delivery in tissue engineering. Adv Drug Deliv Rev 58:515–534

    Article  Google Scholar 

  • Zhang Y, Yu LC (2008) Microinjection as a tool of mechanical delivery. Curr Opin Biotechnol 19:506–510. https://doi.org/10.1016/j.copbio.2008.07.005

    Article  Google Scholar 

  • Zhang Y, Ballas CB, Rao MP (2012) Towards ultrahigh throughput microinjection: MEMS-based massively-parallelized mechanoporation. Proc Annu Int Conf IEEE Eng Med Biol Soc EMBS 594–597. https://doi.org/10.1109/EMBC.2012.6346001

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Acknowledgments

The authors greatly appreciate the financial support from Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India, and Wellcome Trust/DBT India Alliance Fellowship under grant no ECR/2016/001945 and IA/E/16/1/503062. We acknowledge all authors and publishers from whom we received the copyright permissions.

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  1. Amogh Kumar and L. Mohan have contributed equally to this work.

Authors and Affiliations

  1. Department of Engineering Design, Indian Institute of Technology Madras, Chennai, India

    Amogh Kumar, L. Mohan, Pallavi Shinde & Tuhin Subhra Santra

  2. Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan

    Hwan-You Chang

  3. Department of Mechanical Engineering, Toyohashi University of Technology, Toyohashi, Japan

    Moeto Nagai

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  1. Amogh Kumar
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  2. L. Mohan
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  3. Pallavi Shinde
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  4. Hwan-You Chang
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  5. Moeto Nagai
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  6. Tuhin Subhra Santra
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Correspondence to Tuhin Subhra Santra .

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Editors and Affiliations

  1. Department of Engineering Design, Indian Institute of Technology Madras, Chennai, India

    Tuhin Subhra Santra

  2. Department of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan

    Fan-Gang Tseng

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Kumar, A., Mohan, L., Shinde, P., Chang, HY., Nagai, M., Santra, T.S. (2018). Mechanoporation: Toward Single Cell Approaches. In: Santra, T., Tseng, FG. (eds) Handbook of Single Cell Technologies. Springer, Singapore. https://doi.org/10.1007/978-981-10-4857-9_3-1

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  • DOI: https://doi.org/10.1007/978-981-10-4857-9_3-1

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  • Print ISBN: 978-981-10-4857-9

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