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Reduction of Erythrocyte Fluid Adaptability Due to Cell Membrane Hardening Based on Single-Cell Analysis

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Abstract

Because of the rapid development of precision medicine, single-cell analysis has attracted increasing research attention, especially for erythrocyte, whose potential role in the formation of vascular plaque (atherosclerosis) has emphasized the importance of flow characteristics of single erythrocytes in bionic microfluidics. Based on the high incidence of vascular plaques among the elderly and those who have received blood transfusions, we hypothesized that cell membrane hardening changes the fluid adaptability of individual erythrocytes. This hypothesis was verified using an in vitro microfluidic technique based on an analysis of the flow morphology and cell trajectory of individual cells. A symmetrical microchannel was fabricated with a central stenosis to simulate a blood vessel containing plaque. During flowing through this microchannel, normal erythrocyte predominantly exhibited deforming, rotating, and lifting morphologies, resulting in discontinuous contact with the channel wall and a narrower distribution. Conversely, hardened erythrocytes exhibited rolling, swinging, and tumbling morphologies, resulting in stable and continuous contact with the channel wall and a wider distribution. These results indicate that cell membrane hardening decrease cell fluid adaptability on a microscopic scale. This research can offer some new insights into vascular plaques research from a bio-tribological and mechanical perspectives.

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References

  1. Paramo, J.A., Varea, S., Lecumberri, R.: Thrombosis and antithrombotic therapy in the elderly. Med. Clin. 137, 468–471 (2011)

    Article  Google Scholar 

  2. Murat, B., Semih, C., Naside, G.D., Ronald, W.D., Lars, M.S., Utkan, D.: Integrating cell phone imaging with magnetic levitation (i-LEV) for label-free blood analysis at the point-of-living. Small 12, 1222–1229 (2016)

    Article  Google Scholar 

  3. Yazdani, A., Li, X., Em, K.G.: Dynamic and rheological properties of soft biological cell suspensions. Rheol. Acta. 55, 433–449 (2016)

    Article  CAS  Google Scholar 

  4. Litvinov, R.I., Weisel, J.W.: Role of red blood cells in haemostasis and thrombosis. ISBT Sci Ser. 12, 176–183 (2017)

    Article  CAS  Google Scholar 

  5. Ariens, R.A.S.: Contribution of red blood cells and clot structure to thrombosis. Blood 126, 23–38 (2015)

    Article  Google Scholar 

  6. Byrnes, J.R., Wolberg, A.S.: Red blood cells in thrombosis. Blood 130, 1795–1799 (2017)

    Article  CAS  Google Scholar 

  7. Mackman, N.: The red blood cell death receptor and thrombosis. J. Clin. Investig. 128, 3747–3749 (2018)

    Article  Google Scholar 

  8. Franco, R.S., Estela, M., Puchulu, C., Barber, L.A., Palascak, M.B., Joiner, C.H., Low, P.S., Cohen, R.M.: Changes in the properties of normal human red blood cells during in vivo aging. Am. J. Hematol. 88, 44–51 (2013)

    Article  CAS  Google Scholar 

  9. Chen, Y., Feng, Y., Wan, J., Chen, H.: Enhanced separation of aged RBCs by designing channel cross section. Biomicrofluidics 12, 024106 (2018)

    Article  Google Scholar 

  10. Nesbitt, W.S., Westein, E., Tovar-Lopez, F.J., Tolouei, E., Mitchell, A., Fu, J., Carberry, J., Fouras, A., Jackson, S.P.: A shear gradient-dependent platelet aggregation mechanism drives thrombus formation. Nat. Methods 15, 665–673 (2009)

    CAS  Google Scholar 

  11. Bacher, C., Schrack, L., Gekle, S.: Clustering of microscopic particles in constricted blood flow. Phys. Rev. Fluids 2, 013102 (2017)

    Article  Google Scholar 

  12. Ha, H., Lee, S.J.: Hemodynamic features and platelet aggregation in a stenosed microchannel. Microvasc. Res. 90, 96–105 (2013)

    Article  Google Scholar 

  13. Myungjin, K., Ho, S.J., Kyung, C.K.: In-vitro investigation of RBCs’ flow characteristics and hemodynamic feature through a microchannel with a micro-stenosis. Int. J. Biol. Biomed. Eng. 1, 1–8 (2008)

    Google Scholar 

  14. Chen, H., Zhang, P., Zhang, L., Liu, H., Jiang, Y., Zhang, D., Han, Z., Jiang, L.: Continuous directional water transport on the peristome surface of Nepenthes alata. Nature 532, 85–89 (2016)

    Article  CAS  Google Scholar 

  15. Chen, H., Ran, T., Gan, Y., Zhou, J., Zhang, Y., Zhang, L., Zhang, D., Jiang, L.: Ultrafast water harvesting and transport in hierarchical microchannels. Nat. Mater. 17, 935–942 (2018)

    Article  CAS  Google Scholar 

  16. Mancuso, J.E., Ristenpart, W.D.: Stretching of red blood cells at high strain rates. Phys. Rev. Fluids 2, 101101 (2017)

    Article  Google Scholar 

  17. Zeng, N.F., Ristenpart, W.D.: Mechanical response of red blood cells entering a constriction. Biomicrofluidics 8, 064123 (2014)

    Article  Google Scholar 

  18. Abkarian, M., Faivre, M., Viallat, A.: Swinging of red blood cells under shear flow. Phys. Rev. Lett. 98, 188302 (2007)

    Article  Google Scholar 

  19. Doddi, S.K., Bagchi, P.: Three-dimensional computational modeling of multiple deformable cells flowing in microvessels. Phys. Rev. E 79, 046318 (2009)

    Article  Google Scholar 

  20. Dupire, J., Socol, M., Viallat, A.: Full dynamics of a red blood cell in shear flow. Proc. Natl. Acad. Sci. 109, 20808–20813 (2012)

    Article  CAS  Google Scholar 

  21. Zhang, X.B., Wu, Z.Q., Wang, K., Zhu, J., Xu, J.J., Xia, X.H., Chen, H.Y.: Gravitational sedimentation induced blood de lamination for continuous plasma separation on a microfluidics chip. Anal. Chem. 84, 780–3786 (2012)

    Google Scholar 

  22. Chen, Y., Li, Y., Li, D., Li, J., Chen, H.: Margination mechanism of hardened red blood cell in microchannel with different cross-section shapes. Microfluid. Nanofluid. 23, 1–10 (2019)

    Article  CAS  Google Scholar 

  23. Abkarian, M., Viallat, A.: Dynamics of vesicles in a wall-bounded shear flow. Biophys. J. 89, 1055–1066 (2005)

    Article  CAS  Google Scholar 

  24. Chen, Y., Li, D., Li, Y., Wan, J., Li, J., Chen, H.: Margination of hardened red blood cells regulated by vessel geometry. Sci. Rep. 7, 15253 (2017)

    Article  Google Scholar 

  25. Rao, D.S., Goldin, J.G., Fishbein, M.C.: Determinants of plaque instability in atherosclerotic vascular disease. Cardiovasc. Pathol. 14, 285–293 (2005)

    Article  Google Scholar 

  26. Secomb, T.W., Hsu, R., Pries, A.R.: Motion of red blood cells in a capillary with an endothelial surface layer: effect of flow velocity. Am. J. Physiol. Heart Circ. Physiol. 281, H629 (2001)

    Article  CAS  Google Scholar 

  27. Forsyth, A.M., Wan, J., Ristenpart, W.D., Stone, H.A.: The dynamic behavior of chemically “hardened” red blood cells in microchannel flows. Microvasc. Res. 80, 37–43 (2010)

    Article  CAS  Google Scholar 

  28. Forsyth, A.M., Wan, J., Owrutsky, P.D., Abkarian, M., Stone, H.A.: Multiscale approach to link red blood cell dynamics, shear viscosity, and ATP release. Proc. Natl. Acad. Sci. 108, 10986–10991 (2011)

    Article  CAS  Google Scholar 

  29. Tomaiuolo, G., Guido, S.: Start-up shape dynamics of red blood cells in microcapillary flow. Microvasc. Res. 82, 35–41 (2011)

    Article  Google Scholar 

  30. Tomaiuolo, G.: Biomechanical properties of red blood cells in health and disease towards microfluidics. Biomicrofluidics 8, 051501 (2014)

    Article  Google Scholar 

  31. Shelby, J.P., White, J., Ganesan, K., Rathod, K.P., Chiu, T.D.: A microfluidic model for single-cell capillary obstruction by Plasmodiumfalciparum-infected erythrocytes. Proc. Natl. Acad. Sci. 100, 4618–14622 (2003)

    Article  Google Scholar 

  32. Kim, G.Y., Han, J., Park, J.K.: Inertial microfluidics-based cell sorting. BioChip J. 12, 257–267 (2018)

    Article  Google Scholar 

  33. Lee, H., Purdon, A.M., Westervelt, R.M.: Manipulation of biological cells using a microelectromagnet matrix. Appl. Phys. Lett. 85, 1063–1065 (2004)

    Article  CAS  Google Scholar 

  34. David, G.G.: A revolution in optical manipulation. Nature 424, 810–816 (2003)

    Article  Google Scholar 

  35. Mcdonald, J.C., Duffy, D.C., Anderson, J.R., Chiu, T.D., Wu, H., Schueller, J.A.O., Whitesides, M.G.: Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis 21, 27–40 (2000)

    Article  CAS  Google Scholar 

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Acknowledgements

This work is supported by the National Natural Science Foundation of China (Grants Nos. 51322501, 52005019 and 51420105006), and the Project funded by China Postdoctoral Science Foundation (No. 2019M650419). the National Science Fund for Distinguished Young Scholars (No. 51725501), the National Natural Science Foundation of China (Key Program, No. 51935001), and the National Key R&D Program of China (No. 2019YFB1309702). We thank Bing Dong for his support on this work, and thank Yu Lei for his help on English grammar.

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HSC conceived the idea and designed the experiment, YYC and ZNL carried out the experiments and analyzed the data. YYC wrote the paper. XB, YMF helped draw the figures. LF helped revise the paper. DYZ and HWC contributed to scientific discussion of the article. YYC and ZNL contributed equally to this work.

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Correspondence to Haosheng Chen.

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The authors declare no competing financial interests.

Supplementary Information

Below is the link to the electronic supplementary material.

13206_2021_5_MOESM1_ESM.docx

See supplementary material for the experimental details, modulus of erythrocytes with different state, the image processing details, and the erythrocytes flowed in narrower microchannel. (DOCX 1821 KB)

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Chen, Y., Li, Z., Bai, X. et al. Reduction of Erythrocyte Fluid Adaptability Due to Cell Membrane Hardening Based on Single-Cell Analysis. BioChip J 15, 90–99 (2021). https://doi.org/10.1007/s13206-021-00005-4

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  • DOI: https://doi.org/10.1007/s13206-021-00005-4

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