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Single-Cell Mechanical Properties: Label-Free Biomarkers for Cell Status Evaluation

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Essentials of Single-Cell Analysis

Part of the book series: Series in BioEngineering ((SERBIOENG))

Abstract

The mechanical behavior of biological cells is largely determined by their cytoskeletons; abnormal cellular functions can change cytoskeletons, leading to variations in cellular mechanical properties. This chapter begins with a summary of the relationships between cellular mechanical properties and various disease processes and changes in cell states: (1) changes in stiffness of red blood cells in cytoskeletal disorders, such as malaria and sickle cell anemia; (2) increased cell deformability of invasive cancer cells, compared with benign counterparts; (3) increased stiffness of leukocytes in sepsis; and (4) decreased deformability during the stem cell differentiation process. In the following section, we discuss the well-established techniques that are being used to measure the mechanical properties of single cells, including atomic force microscopy and micropipette aspiration. Finally, we describe the microfluidic approaches—including microfluidic constriction channels, microfluidic optical stretchers, and microfluidic hydrodynamic stretchers—that are being developed as next-generation, automated, and high-throughput techniques for characterization of the mechanical properties of single cells. The advantages and limitations of each technique are compared and future research opportunities are highlighted.

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References

  1. Ethier CR, Simmons CA (2007) Introductory biomechanics: from cells to organisms. Cambridge texts in biomedical engineering, vol xiii. Cambridge University Press, Cambridge, 511 p, [16] p. of plates

    Google Scholar 

  2. Fletcher DA, Mullins RD (2010) Cell mechanics and the cytoskeleton. Nature 463(7280):485–492

    Article  Google Scholar 

  3. Lim CT, Zhou EH, Quek ST (2006) Mechanical models for living cells—a review. J Biomech 39(2):195–216

    Article  Google Scholar 

  4. Di Carlo D (2012) A mechanical biomarker of cell state in medicine. J Lab Autom 17(1):32–42

    Article  Google Scholar 

  5. Lee GYH, Lim CT (2007) Biomechanics approaches to studying human diseases. Trends Biotechnol 25(3):111–118

    Article  MathSciNet  Google Scholar 

  6. Diez-Silva M et al (2010) Shape and biomechanical characteristics of human red blood cells in health and disease. MRS Bull 35(5):382–388

    Article  Google Scholar 

  7. Lim CT, Li A (2011) Mechanopathology of red blood cell diseases—Why mechanics matters. Theor Appl Mech Lett 1(1):014000

    Article  Google Scholar 

  8. Suresh S (2007) Biomechanics and biophysics of cancer cells. Acta Biomater 3(4):413–438

    Article  Google Scholar 

  9. Katira P, Bonnecaze RT, Zaman MH (2013) Modeling the mechanics of cancer: effect of changes in cellular and extra-cellular mechanical properties. Front Oncol 3:145

    Article  Google Scholar 

  10. Zhang W et al (2013) A brief review of the biophysical hallmarks of metastatic cancer cells. Cancer Hallm 1(2–3):59–66

    Article  Google Scholar 

  11. Kovach MA, Standiford TJ (2012) The function of neutrophils in sepsis. Curr Opin Infect Dis 25(3):321–327

    Article  Google Scholar 

  12. Keefer CL, Desai JP (2011) Mechanical phenotyping of stem cells. Theriogenology 75(8):1426–1430

    Article  Google Scholar 

  13. Li D et al (2011) Role of mechanical factors in fate decisions of stem cells. Regenerative Med 6(2):229–240

    Article  Google Scholar 

  14. Discher DE, Mooney DJ, Zandstra PW (2009) Growth factors, matrices, and forces combine and control stem cells. Science 324(5935):1673–1677

    Article  Google Scholar 

  15. Lehenkari PP et al (2000) Adapting atomic force microscopy for cell biology. Ultramicroscopy 82(1–4):289–295

    Article  Google Scholar 

  16. Charras GT, Horton MA (2002) Single cell mechanotransduction and its modulation analyzed by atomic force microscope indentation. Biophys J 82(6):2970–2981

    Article  Google Scholar 

  17. Radmacher M (2002) Measuring the elastic properties of living cells by the atomic force microscope. Methods Cell Biol 68:67–90

    Article  Google Scholar 

  18. Alonso JL, Goldmann WH (2003) Feeling the forces: atomic force microscopy in cell biology. Life Sci 72(23):2553–2560

    Article  Google Scholar 

  19. Costa KD (2003) Single-cell elastography: probing for disease with the atomic force microscope. Dis Markers 19(2–3):139–154

    Google Scholar 

  20. Costa KD (2006) Imaging and probing cell mechanical properties with the atomic force microscope. Methods Mol Biol 319:331–361

    Article  Google Scholar 

  21. Kuznetsova TG et al (2007) Atomic force microscopy probing of cell elasticity. Micron 38(8):824–833

    Article  Google Scholar 

  22. Lekka M, Laidler P (2009) Applicability of AFM in cancer detection. Nat Nanotechnol 4(2):72

    Article  Google Scholar 

  23. Kirmizis D, Logothetidis S (2010) Atomic force microscopy probing in the measurement of cell mechanics. Int J Nanomed 5:137–145

    Article  Google Scholar 

  24. Shi X et al (2012) Living cell study at the single-molecule and single-cell levels by atomic force microscopy. Nanomedicine 7(10):1625–1637

    Article  Google Scholar 

  25. Hochmuth RM (2000) Micropipette aspiration of living cells. J Biomech 33(1):15–22

    Article  Google Scholar 

  26. Kim DH et al (2009) Microengineered platforms for cell mechanobiology. Annu Rev Biomed Eng 11:203–233

    Article  Google Scholar 

  27. Zheng Y, Sun Y (2011) Microfluidic devices for mechanical characterisation of single cells in suspension. Micro Nano Lett 6(5):327–331

    Article  MathSciNet  Google Scholar 

  28. Mao X, Huang TJ (2012) Exploiting mechanical biomarkers in microfluidics. Lab Chip 12(20):4006–4009

    Article  Google Scholar 

  29. Zheng Y et al (2013) Recent advances in microfluidic techniques for single-cell biophysical characterization. Lab Chip 13(13):2464–2483

    Article  Google Scholar 

  30. White NJ et al (2014) Malaria. Lancet 383(9918):723–735

    Article  Google Scholar 

  31. Grayson M (2012) Malaria. Nature 484(7395):1

    Article  Google Scholar 

  32. Miller LH et al (2002) The pathogenic basis of malaria. Nature 415(6872):673–679

    Article  Google Scholar 

  33. Suresh S et al (2005) Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria. Acta Biomater 1(1):15–30

    Article  MathSciNet  Google Scholar 

  34. Nash GB et al (1989) Abnormalities in the mechanical properties of red blood cells caused by Plasmodium falciparum. Blood 74(2):855–861

    Google Scholar 

  35. Paulitschke M, Nash GB (1993) Membrane rigidity of red blood cells parasitized by different strains of Plasmodium falciparum. J Lab Clin Med 122(5):581–589

    Google Scholar 

  36. Glenister FK et al (2002) Contribution of parasite proteins to altered mechanical properties of malaria-infected red blood cells. Blood 99(3):1060–1063

    Article  Google Scholar 

  37. Mills JP et al (2004) Nonlinear elastic and viscoelastic deformation of the human red blood cell with optical tweezers. Mech Chem Biosyst 1(3):169–180

    Google Scholar 

  38. Bambardekar K et al (2008) Measuring erythrocyte deformability with fluorescence, fluid forces, and optical trapping. J Biomed Opt 13(6):064021

    Article  Google Scholar 

  39. Shelby JP et al (2003) A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum infected erythrocytes. Proc Natl Acad Sci USA 100(25):14618–14622

    Article  Google Scholar 

  40. Handayani S et al (2009) High deformability of Plasmodium vivax-infected red blood cells under microfluidic conditions. J Infect Dis 199(3):445–450

    Article  Google Scholar 

  41. Bow H et al (2011) A microfabricated deformability-based flow cytometer with application to malaria. Lab Chip 11(6):1065–1073

    Article  Google Scholar 

  42. Rees DC, Williams TN, Gladwin MT (2010) Sickle-cell disease. Lancet 376(9757):2018–2031

    Article  Google Scholar 

  43. Cancado RD (2012) Sickle cell disease: looking back but towards the future. Rev Bras Hematol Hemoter 34(3):175–177

    Article  Google Scholar 

  44. Darlison MW, Modell B (2013) Sickle-cell disorders: limits of descriptive epidemiology. Lancet 381(9861):98–99

    Article  Google Scholar 

  45. Fottrell E, Osrin D (2013) Sickle cell anaemia in a changing world. PLoS Med 10(7):e1001483

    Article  Google Scholar 

  46. Evans E, Mohandas N, Leung A (1984) Static and dynamic rigidities of normal and sickle erythrocytes. Major influence of cell hemoglobin concentration. J Clin Invest 73(2):477–488

    Article  Google Scholar 

  47. Nash GB, Johnson CS, Meiselman HJ (1984) Mechanical properties of oxygenated red blood cells in sickle cell (HbSS) disease. Blood 63(1):73–82

    Google Scholar 

  48. Nash GB, Johnson CS, Meiselman HJ (1986) Influence of oxygen tension on the viscoelastic behavior of red blood cells in sickle cell disease. Blood 67(1):110–118

    Google Scholar 

  49. Evans EA, Mohandas N (1987) Membrane-associated sickle hemoglobin: a major determinant of sickle erythrocyte rigidity. Blood 70(5):1443–1449

    Google Scholar 

  50. Itoh T, Chien S, Usami S (1992) Deformability measurements on individual sickle cells using a new system with pO2 and temperature control. Blood 79(8):2141–2147

    Google Scholar 

  51. Itoh T, Chien S, Usami S (1995) Effects of hemoglobin concentration on deformability of individual sickle cells after deoxygenation. Blood 85(8):2245–2253

    Google Scholar 

  52. Barabino GA, Platt MO, Kaul DK (2010) Sickle cell biomechanics. Annu Rev Biomed Eng 12:345–367

    Article  Google Scholar 

  53. Ballas SK, Mohandas N (2004) Sickle red cell microrheology and sickle blood rheology. Microcirculation 11(2):209–225

    Article  Google Scholar 

  54. Ferlay J et al (2015) Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386

    Article  Google Scholar 

  55. Ruddon RW (2007) Cancer biology, vol xiv, 4th ed. Oxford University Press, New York, 530 p

    Google Scholar 

  56. Weinberg RA (2007) The biology of cancer. Garland Science, Taylor and Francis, New York, London

    Google Scholar 

  57. Jonietz E (2012) Mechanics: the forces of cancer. Nature 491(7425):S56–S57

    Article  Google Scholar 

  58. Ward KA et al (1991) Viscoelastic properties of transformed cells: role in tumor cell progression and metastasis formation. Biorheology 28(3–4):301–313

    Google Scholar 

  59. Thoumine O, Ott A (1997) Comparison of the mechanical properties of normal and transformed fibroblasts. Biorheology 34(4–5):309–326

    Article  Google Scholar 

  60. Wu ZZ et al (2000) Comparison of the viscoelastic properties of normal hepatocytes and hepatocellular carcinoma cells under cytoskeletal perturbation. Biorheology 37(4):279–290

    Google Scholar 

  61. Zhang G et al (2002) Mechanical properties of hepatocellular carcinoma cells. World J Gastroenterol 8(2):243–246

    Google Scholar 

  62. Anderson K et al (1991) In vitro studies of deformation and adhesion properties of transformed cells. Cell Biophys 18(2):81–97

    Article  Google Scholar 

  63. Saab MB et al (2013) Differential effect of curcumin on the nanomechanics of normal and cancerous Mammalian epithelial cells. Cell Biochem Biophys 65(3):399–411

    Article  Google Scholar 

  64. Sarna M et al (2013) Nanomechanical analysis of pigmented human melanoma cells. Pigm Cell Melanoma Res 26(5):727–730

    Article  Google Scholar 

  65. Andolfi L et al (2014) Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy. PLoS One 9(11):e112582

    Article  Google Scholar 

  66. Liu H et al (2014) Biophysical characterization of bladder cancer cells with different metastatic potential. Cell Biochem Biophys 68(2):241–246

    Article  Google Scholar 

  67. Omidvar R et al (2014) Atomic force microscope-based single cell force spectroscopy of breast cancer cell lines: an approach for evaluating cellular invasion. J Biomech 47(13):3373–3379

    Article  MathSciNet  Google Scholar 

  68. Osmulski P et al (2014) Nanomechanical biomarkers of single circulating tumor cells for detection of castration resistant prostate cancer. Prostate 74(13):1297–1307

    Article  Google Scholar 

  69. Ramos JR et al (2014) The softening of human bladder cancer cells happens at an early stage of the malignancy process. Beilstein J Nanotechnol 5:447–457

    Article  Google Scholar 

  70. Rother J et al (2014) Atomic force microscopy-based microrheology reveals significant differences in the viscoelastic response between malign and benign cell lines. Open Biology 4(5):140046

    Article  Google Scholar 

  71. Xu W et al (2012) Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells. PLoS One 7(10):e46609

    Article  Google Scholar 

  72. Watanabe T et al (2012) Higher cell stiffness indicating lower metastatic potential in B16 melanoma cell variants and in (−)-epigallocatechin gallate-treated cells. J Cancer Res Clin Oncol 138:859–866

    Article  Google Scholar 

  73. Plodinec M et al (2012) The nanomechanical signature of breast cancer. Nat Nanotechnol 7(11):757–765

    Article  Google Scholar 

  74. Lekka M et al (2012) Cancer cell recognition–mechanical phenotype. Micron 43(12):1259–1266

    Article  Google Scholar 

  75. Ketene AN et al (2012) The effects of cancer progression on the viscoelasticity of ovarian cell cytoskeleton structures. Nanomedicine 8(1):93–102

    Google Scholar 

  76. Bastatas L et al (2012) AFM nano-mechanics and calcium dynamics of prostate cancer cells with distinct metastatic potential. Biochim Biophys Acta 1820(7):1111–1120

    Article  Google Scholar 

  77. Jonas O, Mierke CT, Kas JA (2011) Invasive cancer cell lines exhibit biomechanical properties that are distinct from their noninvasive counterparts. Soft Matter 7(24):11488–11495

    Article  Google Scholar 

  78. Cross SE et al (2011) Green tea extract selectively targets nanomechanics of live metastatic cancer cells. Nanotechnology 22(21):215101

    Article  Google Scholar 

  79. Wang J et al (2009) Atomic force microscope study of tumor cell membranes following treatment with anti-cancer drugs. Biosens Bioelectron 25(4):721–727

    Article  Google Scholar 

  80. Iyer S et al (2009) Atomic force microscopy detects differences in the surface brush of normal and cancerous cells. Nat Nanotechnol 4(6):389–393

    Article  Google Scholar 

  81. Lekka M et al (1999) Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy. Eur Biophys J 28(4):312–316

    Article  Google Scholar 

  82. Lekka M et al (2001) The effect of chitosan on stiffness and glycolytic activity of human bladder cells. Biochim Biophys Acta 1540(2):127–136

    Article  Google Scholar 

  83. Cross SE et al (2007) Nanomechanical analysis of cells from cancer patients. Nat Nanotechnol 2(12):780–783

    Article  Google Scholar 

  84. Cross SE et al (2008) AFM-based analysis of human metastatic cancer cells. Nanotechnology 19(38):384003

    Article  Google Scholar 

  85. Docheva D et al (2010) Effect of collagen I and fibronectin on the adhesion, elasticity and cytoskeletal organization of prostate cancer cells. Biochem Biophys Res Commun 402(2):361–366

    Article  Google Scholar 

  86. Tang X et al (2014) A mechanically-induced colon cancer cell population shows increased metastatic potential. Molecular Cancer 13:131

    Article  Google Scholar 

  87. Faria EC et al (2008) Measurement of elastic properties of prostate cancer cells using AFM. Analyst 133(11):1498–1500

    Article  Google Scholar 

  88. Li QS et al (2008) AFM indentation study of breast cancer cells. Biochem Biophys Res Commun 374(4):609–613

    Article  Google Scholar 

  89. Leporatti S et al (2009) Cytomechanical and topological investigation of MCF-7 cells by scanning force microscopy. Nanotechnology 20(5):055103

    Article  Google Scholar 

  90. Fuhrmann A et al (2011) AFM stiffness nanotomography of normal, metaplastic and dysplastic human esophageal cells. Phys Biol 8(1):015007

    Article  Google Scholar 

  91. Coughlin MF et al (2013) Cytoskeletal stiffness, friction, and fluidity of cancer cell lines with different metastatic potential. Clin Exp Metastas 30(3):237–250

    Article  Google Scholar 

  92. Lincoln B et al (2004) Deformability-based flow cytometry. Cytometry Part A 59A(2):203–209

    Article  Google Scholar 

  93. Guck J et al (2005) Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys J 88(5):3689–3698

    Article  Google Scholar 

  94. Mak M, Erickson D (2013) A serial micropipette microfluidic device with applications to cancer cell repeated deformation studies. Integr Biology 5(11):1374–1384

    Article  Google Scholar 

  95. Khan ZS, Vanapalli SA (2013) Probing the mechanical properties of brain cancer cells using a microfluidic cell squeezer device. Biomicrofluidics 7(1):11806

    Article  Google Scholar 

  96. Byun S et al (2013) Characterizing deformability and surface friction of cancer cells. Proc Natl Acad Sci 110(19):7580–7585

    Article  Google Scholar 

  97. Hou HW et al (2009) Deformability study of breast cancer cells using microfluidics. Biomed Microdevices 11(3):557–564

    Article  Google Scholar 

  98. Gossett DR et al (2012) Hydrodynamic stretching of single cells for large population mechanical phenotyping. Proc Natl Acad Sci USA 109(20):7630–7635

    Article  Google Scholar 

  99. Hotchkiss RS, Karl IE (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348(2):138–150

    Article  Google Scholar 

  100. Bone RC (1991) The pathogenesis of sepsis. Ann Intern Med 115(6):457–469

    Article  Google Scholar 

  101. Yodice PC et al (1997) Neutrophil rheologic changes in septic shock. Am J Respir Crit Care Med 155(1):38–42

    Article  Google Scholar 

  102. Alves-Filho JC et al (2008) The role of neutrophils in severe sepsis. Shock 30(Suppl 1):3–9

    Article  Google Scholar 

  103. Worthen GS et al (1989) Mechanics of stimulated neutrophils: cell stiffening induces retention in capillaries. Science 245(4914):183–186

    Article  Google Scholar 

  104. Poschl JM, Ruef P, Linderkamp O (2005) Deformability of passive and activated neutrophils in children with Gram-negative septicemia. Scand J Clin Lab Invest 65(4):333–339

    Article  Google Scholar 

  105. Skoutelis AT et al (2000) Neutrophil deformability in patients with sepsis, septic shock, and adult respiratory distress syndrome. Crit Care Med 28(7):2355–2359

    Article  Google Scholar 

  106. Linderkamp O et al (1998) Passive deformability of mature, immature, and active neutrophils in healthy and septicemic neonates. Pediatr Res 44(6):946–950

    Article  Google Scholar 

  107. Inoue Y et al (2006) A neutrophil elastase inhibitor, sivelestat, improves leukocyte deformability in patients with acute lung injury. J Trauma 60(5):936–943

    Article  Google Scholar 

  108. Nishino M et al (2005) Serial changes in leukocyte deformability and whole blood rheology in patients with sepsis or trauma. J Trauma 59(6):1425–1431

    Article  MathSciNet  Google Scholar 

  109. Tanaka H et al (2001) Granulocyte colony-stimulating factor (G-CSF) stiffens leukocytes but attenuates inflammatory response without lung injury in septic patients. J Trauma 51(6):1110–1116

    Article  Google Scholar 

  110. Lovell-Badge R (2001) The future for stem cell research. Nature 414(6859):88–91

    Article  Google Scholar 

  111. Krupalnik V, Hanna JH (2014) Stem cells: The quest for the perfect reprogrammed cell. Nature 511(7508):160–162

    Article  Google Scholar 

  112. Chamberlain JS (2006) Stem-cell biology: a move in the right direction. Nature 444(7119):552–553

    Article  Google Scholar 

  113. Tan SC et al (2008) Viscoelastic behaviour of human mesenchymal stem cells. BMC Cell Biology 9:40

    Article  Google Scholar 

  114. Yu H et al (2010) Mechanical behavior of human mesenchymal stem cells during adipogenic and osteogenic differentiation. Biochem Biophys Res Commun 393(1):150–155

    Article  Google Scholar 

  115. Khani MM et al (2014) Evaluation of mechanical properties of human mesenchymal stem cells during differentiation to smooth muscle cells. Ann Biomed Eng 42(7):1373–1380

    Article  Google Scholar 

  116. Darling EM et al (2008) Viscoelastic properties of human mesenchymally-derived stem cells and primary osteoblasts, chondrocytes, and adipocytes. J Biomech 41(2):454–464

    Article  Google Scholar 

  117. Pillarisetti A et al (2011) Mechanical phenotyping of mouse embryonic stem cells: increase in stiffness with differentiation. Cell Reprogram 13(4):371–380

    Article  Google Scholar 

  118. Ruiz JP et al (2012) The effect of nicotine on the mechanical properties of mesenchymal stem cells. Cell Health Cytoskelet 4:29–35

    Google Scholar 

  119. Aryaei A, Jayasuriya AC (2013) Mechanical properties of human amniotic fluid stem cells using nanoindentation. J Biomech 46(9):1524–1530

    Article  Google Scholar 

  120. Hu K, Zhao F, Wang Q (2013) Mechanical characterization of living and dead undifferentiated human adipose-derived stem cells by using atomic force microscopy. Proc Inst Mech Eng [H]: J Eng Med 227(12):1319–1323

    Article  Google Scholar 

  121. Ofek G et al (2009) Mechanical characterization of differentiated human embryonic stem cells. J Biomech Eng 131(6):061011

    Article  Google Scholar 

  122. Van Vliet KJ, Bao G, Suresh S (2003) The biomechanics toolbox: experimental approaches for living cells and biomolecules. Acta Mater 51(19):5881–5905

    Article  Google Scholar 

  123. Lim CT et al (2006) Experimental techniques for single cell and single molecule biomechanics. Mater Sci Eng, C 26(8):1278–1288

    Article  Google Scholar 

  124. Addae-Mensah KA, Wikswo JP (2008) Measurement techniques for cellular biomechanics in vitro. Exp Biol Med 233(7):792–809

    Article  Google Scholar 

  125. Guo Q et al (2012) Characterization of cell elasticity correlated with cell morphology by atomic force microscope. J Biomech 45(2):304–309

    Article  Google Scholar 

  126. Pogoda K et al (2012) Depth-sensing analysis of cytoskeleton organization based on AFM data. Eur Biophys J 41(1):79–87

    Article  Google Scholar 

  127. Lekka M et al (2012) Cancer cell detection in tissue sections using AFM. Arch Biochem Biophys 518(2):151–156

    Article  Google Scholar 

  128. Shojaei-Baghini E et al (2013) Mechanical characterization of benign and malignant urothelial cells from voided urine. Appl Phys Lett 102(12):123704

    Article  Google Scholar 

  129. Shojaei-Baghini E, Zheng Y, Sun Y (2013) Automated micropipette aspiration of single cells. Ann Biomed Eng 41(6):1208–1216

    Article  Google Scholar 

  130. Wootton RC, Demello AJ (2010) Microfluidics: exploiting elephants in the room. Nature 464(7290):839–840

    Article  Google Scholar 

  131. Whitesides GM (2006) The origins and the future of microfluidics. Nature 442(7101):368–373

    Article  Google Scholar 

  132. Squires TM, Quake SR (2005) Microfluidics: fluid physics at the nanoliter scale. Rev Mod Phys 77(3):977

    Article  Google Scholar 

  133. Sackmann EK, Fulton AL, Beebe DJ (2014) The present and future role of microfluidics in biomedical research. Nature 507(7491):181–189

    Article  Google Scholar 

  134. El-Ali J, Sorger PK, Jensen KF (2006) Cells on chips. Nature 442(7101):403–411

    Article  Google Scholar 

  135. Meyvantsson I, Beebe DJ (2008) Cell culture models in microfluidic systems. Annu Rev Anal Chem 1:423–449

    Article  Google Scholar 

  136. Paguirigan AL, Beebe DJ (2008) Microfluidics meet cell biology: bridging the gap by validation and application of microscale techniques for cell biological assays. BioEssays 30(9):811–821

    Article  Google Scholar 

  137. Velve-Casquillas G et al (2010) Microfluidic tools for cell biological research. Nano Today 5(1):28–47

    Article  Google Scholar 

  138. Thompson AM et al (2014) Microfluidics for single-cell genetic analysis. Lab Chip 14(17):3135–3142

    Article  Google Scholar 

  139. Yin H, Marshall D (2012) Microfluidics for single cell analysis. Curr Opin Biotechnol 23(1):110–119

    Article  Google Scholar 

  140. Lecault V et al (2012) Microfluidic single cell analysis: from promise to practice. Curr Opin Chem Biol 16(3–4):381–390

    Article  Google Scholar 

  141. Ryan D, Ren K, Wu H (2011) Single-cell assays. Biomicrofluidics 5(2):21501

    Article  Google Scholar 

  142. Zare RN, Kim S (2010) Microfluidic platforms for single-cell analysis. Annu Rev Biomed Eng 12:187–201

    Article  Google Scholar 

  143. Sims CE, Allbritton NL (2007) Analysis of single mammalian cells on-chip. Lab Chip 7(4):423–440

    Article  Google Scholar 

  144. Di Carlo D, Lee LP (2006) Dynamic single-cell analysis for quantitative biology. Anal Chem 78(23):7918–7925

    Article  Google Scholar 

  145. Quinn DJ et al (2011) Combined simulation and experimental study of large deformation of red blood cells in microfluidic systems. Ann Biomed Eng 39(3):1041–1050

    Article  Google Scholar 

  146. Diez-Silva M et al (2012) Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells. Sci Rep 2:614

    Article  Google Scholar 

  147. Zheng Y et al (2012) High-throughput biophysical measurement of human red blood cells. Lab Chip 12(14):2560–2567

    Article  Google Scholar 

  148. Huang S et al (2013) Dynamic deformability of Plasmodium falciparum-infected erythrocytes exposed to artesunate in vitro. Integr Biol 5(2):414–422

    Article  Google Scholar 

  149. Wu T, Feng JJ (2013) Simulation of malaria-infected red blood cells in microfluidic channels: passage and blockage. Biomicrofluidics 7(4):44115

    Article  MathSciNet  Google Scholar 

  150. Zheng Y et al (2013) Electrical measurement of red blood cell deformability on a microfluidic device. Lab Chip 13(16):3275–3283

    Article  Google Scholar 

  151. Zheng Y et al (2014) Characterization of red blood cell deformability change during blood storage. Lab Chip 14(3):577–583

    Article  Google Scholar 

  152. Myrand-Lapierre M-E et al (2015) Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability. Lab Chip 15(1):159–167

    Article  Google Scholar 

  153. Rosenbluth MJ, Lam WA, Fletcher DA (2008) Analyzing cell mechanics in hematologic diseases with microfluidic biophysical flow cytometry. Lab Chip 8(7):1062–1070

    Article  Google Scholar 

  154. Chen J et al (2011) Classification of cell types using a microfluidic device for mechanical and electrical measurement on single cells. Lab Chip 11(18):3174–3181

    Article  Google Scholar 

  155. Lee LM, Liu AP (2015) A microfluidic pipette array for mechanophenotyping of cancer cells and mechanical gating of mechanosensitive channels. Lab Chip 15(1):264–273

    Article  Google Scholar 

  156. Tsai CH et al (2014) A new dimensionless index for evaluating cell stiffness-based deformability in microchannel. IEEE Trans Bio-Med Eng 61(4):1187–1195

    Article  Google Scholar 

  157. Luo YN et al (2014) A constriction channel based microfluidic system enabling continuous characterization of cellular instantaneous Young’s modulus. Sens Actuators B: Chem 202:1183–1189

    Article  Google Scholar 

  158. Guo Q, Park S, Ma H (2012) Microfluidic micropipette aspiration for measuring the deformability of single cells. Lab Chip 12(15):2687–2695

    Article  Google Scholar 

  159. Leong FY et al (2011) Modeling cell entry into a micro-channel. Biomech Model Mechanobiol 10(5):755–766

    Article  MathSciNet  Google Scholar 

  160. Guo Q et al (2012) Microfluidic biomechanical assay for red blood cells parasitized by Plasmodium falciparum. Lab Chip 12(6):1143–1150

    Article  Google Scholar 

  161. Beattie W et al (2014) Clog-free cell filtration using resettable cell traps. Lab Chip 14(15):2657–2665

    Article  Google Scholar 

  162. Huang SB et al (2014) A clogging-free microfluidic platform with an incorporated pneumatically-driven membrane-based active valve enabling specific membrane capacitance and cytoplasm conductivity characterization of single cells. Sens Actuators B: Chem 190:928–936

    Article  Google Scholar 

  163. Lautenschlager F et al (2009) The regulatory role of cell mechanics for migration of differentiating myeloid cells. Proc Natl Acad Sci USA 106(37):15696–15701

    Article  Google Scholar 

  164. Remmerbach TW et al (2009) Oral cancer diagnosis by mechanical phenotyping. Cancer Res 69(5):1728–1732

    Article  Google Scholar 

  165. Chen B, Guo F, Xiang H (2011) Visualization study of motion and deformation of red blood cells in a microchannel with straight, divergent and convergent sections. J Biol Phys 37(4):429–440

    Article  Google Scholar 

  166. Forsyth AM et al (2010) The dynamic behavior of chemically “stiffened” red blood cells in microchannel flows. Microvasc Res 80(1):37–43

    Article  MathSciNet  Google Scholar 

  167. Lee SS et al (2009) Extensional flow-based assessment of red blood cell deformability using hyperbolic converging microchannel. Biomed Microdevices 11(5):1021–1027

    Article  Google Scholar 

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Acknowledgment

We thank the National Basic Research Program of China (973 Program, Grant No. 2014CB744600), the National Natural Science Foundation of China (Grant Nos. 61201077, 61431019 and 81261120561), the National High Technology Research and Development Program of China (863 Program, Grant No. 2014AA093408), and the Beijing NOVA Program of Science and Technology for financial support.

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Correspondence to Junbo Wang or Min-Hsien Wu .

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Chen, J. et al. (2016). Single-Cell Mechanical Properties: Label-Free Biomarkers for Cell Status Evaluation. In: Tseng, FG., Santra, T. (eds) Essentials of Single-Cell Analysis. Series in BioEngineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-49118-8_8

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