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Medical & Biological Engineering & Computing

, Volume 57, Issue 1, pp 325–337 | Cite as

Automatic directional analysis of cell fluorescence images and morphological modeling of microfilaments

  • Yue Zhou
  • Huiqi LiEmail author
  • Wanjun Zhang
  • Jiayi Xu
  • Xiaojun Li
  • Baohua Ji
Original Article
  • 99 Downloads

Abstract

Cytoskeleton and nucleus are two important anatomic components in eukaryotic cells. Cell fluorescence images are employed to study their realignment and deformation during cell extrusion. Quantitative analysis and modeling of cell orientation are investigated in this paper. For orientation measurement, alignment orientation of microfilaments is calculated using structure tensor method. Nuclei is segmented and fitted to ellipses in nuclei images. Based on the fitted ellipse, orientation and aspect ratio of each nucleus are computed. A morphological model is proposed to describe the movement of microfilaments quantitatively. The parameters of the model are determined by in-plane stresses obtained by numerical simulation. The proposed automatic orientation measurement algorithms can help to analyze the relationship between cell orientation and stress qualitatively. The proposed morphological model is the first model to quantitatively describe the relationship of microfilament movement with stress. Experimental results show that cell and nucleus tend to align along in-plane maximum shear stress and the proposed morphological model is a reasonable model for cell movement. The modeling of cell behavior under different stress can facilitate biomedical research such as tissue engineering and cancer analysis.

Graphical abstract

Keywords

Microfilaments Nuclei Automatic analysis Morphological modeling 

References

  1. 1.
    Candes EJ, Donoho DL (2004) New tight frames of curvelets and optimal representations of objects with piecewise C-2 singularities. Commun Pure Appl Math 57:219–266.  https://doi.org/10.1002/cpa.10116 CrossRefGoogle Scholar
  2. 2.
    Chen TJ, Wu CC, Su FC (2012) Mechanical models of the cellular cytoskeletal network for the analysis of intracellular mechanical properties and force distributions: a review. Med Eng Phys 34:1375–1386.  https://doi.org/10.1016/j.medengphy.2012.08.007 CrossRefPubMedGoogle Scholar
  3. 3.
    Coughlin MF, Stamenovic D (2003) A prestressed cable network model of the adherent cell cytoskeleton. Biophys J 84:1328–1336CrossRefGoogle Scholar
  4. 4.
    Dvir L, Nissim R, Alvarez-Elizondo MB, Weihs D (2015) Quantitative measures to reveal coordinated cytoskeleton-nucleus reorganization during in vitro invasion of cancer cells. New J Phys 17:043010.  https://doi.org/10.1088/1367-2630/17/4/043010 CrossRefGoogle Scholar
  5. 5.
    Fitzgibbon A, Pilu M, Fisher RB (1999) Direct least square fitting of ellipses. IEEE Trans Pattern Anal 21:476–480.  https://doi.org/10.1109/34.765658 CrossRefGoogle Scholar
  6. 6.
    Fonck E, Feigl GG, Fasel J, Sage D, Unser M, Rufenacht DA, Stergiopulos N (2009) Effect of ageing on elastin functionality in human cerebral arteries. Proceedings of the Asme Summer Bioengineering Conference 2008, Pts a and B, pp 959–960Google Scholar
  7. 7.
    Gruenbaum Y, Wilson KL, Harel A, Goldberg M, Cohen M (2000) Nuclear Lamins—structural proteins with fundamental functions. J Struct Biol 129:313–323.  https://doi.org/10.1006/jsbi.2000.4216 CrossRefPubMedGoogle Scholar
  8. 8.
    Harris C (1988) A combined corner and edge detector. Proc Alvey Vision Conf 1988:147–151Google Scholar
  9. 9.
    Hayakawa K, Sato N, Obinata T (2001) Dynamic reorientation of cultured cells and stress fibers under mechanical stress from periodic stretching. Exp Cell Res 268:104–114.  https://doi.org/10.1006/excr.2001.5270 CrossRefPubMedGoogle Scholar
  10. 10.
    He SJ, Liu CL, Li XJ, Ma SP, Huo B, Ji BH (2015) Dissecting collective cell behavior in polarization and alignment on micropatterned substrates. Biophys J 109:489–500.  https://doi.org/10.1016/j.bpj.2015.06.058 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Imhof BA, Aurrand-Lions M (2004) Adhesion mechanisms regulating the migration of monocytes. Nat Rev Immunol 4:432–444.  https://doi.org/10.1038/nri1375 CrossRefPubMedGoogle Scholar
  12. 12.
    Jean RP, Chen CS, Spector AA (2005) Finite-element analysis of the adhesion-cytoskeleton-nucleus mechanotransduction pathway during endothelial cell rounding: axisymmetric model. J Biomech Eng 127:594–600CrossRefGoogle Scholar
  13. 13.
    Jean RP, Gray DS, Spector AA, Chen CS (2004) Characterization of the nuclear deformation caused by changes in endothelial cell shape. J Biomech Eng 126:552–558CrossRefGoogle Scholar
  14. 14.
    Li CM, Huang R, Ding ZH, Gatenby JC, Metaxas DN, Gore JC (2011) A level set method for image segmentation in the presence of intensity inhomogeneities with application to MRI. IEEE Trans Image Process 20:2007–2016.  https://doi.org/10.1109/Tip.2011.2146190 CrossRefPubMedGoogle Scholar
  15. 15.
    Liu AB, Wu HT, Liu CW, Liu CC, Tang CJ, Tsai IT, Sun CK (2015) Application of multiscale entropy in arterial waveform contour analysis in healthy and diabetic subjects. Med Biol Eng Comput 53:89–98CrossRefGoogle Scholar
  16. 16.
    Liu CL, He SJ, Li XJ, Huo B, Ji BH (2016) Mechanics of cell Mechanosensing on patterned substrate. J Appl Mech T ASME 83:051014.  https://doi.org/10.1115/1.4032907 CrossRefGoogle Scholar
  17. 17.
    Parsons JT, Horwitz AR, Schwartz MA (2010) Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Biol 11:633–643.  https://doi.org/10.1038/nrm2957 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Paul R, Heil P, Spatz JP, Schwarz US (2008) Propagation of mechanical stress through the actin cytoskeleton toward focal adhesions: model and experiment. Biophys J 94:1470–1482.  https://doi.org/10.1529/biophysj.107.108688 CrossRefPubMedGoogle Scholar
  19. 19.
    Rezakhaniha R, Agianniotis A, Schrauwen JTC, Griffa A, Sage D, Bouten CVC, van de Vosse FN, Unser M, Stergiopulos N (2012) Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy. Biomech Model Mechanobiol 11:461–473.  https://doi.org/10.1007/s10237-011-0325-z CrossRefPubMedGoogle Scholar
  20. 20.
    Ruggiero C, Giacomini M, Rolfe P (1999) Qualitative modelling of the response of cytoskeletal actin filaments in endothelial cells subjected to shear stress. Med Biol Eng Comput 37:659–666CrossRefGoogle Scholar
  21. 21.
    Sauer RA (2009) Multiscale modelling and simulation of the deformation and adhesion of a single gecko seta. Comput Methods Biomech Biomed Engin 12:627–640.  https://doi.org/10.1080/10255840902802917 CrossRefPubMedGoogle Scholar
  22. 22.
    Schmid C, Mohr R, Bauckhage C (2000) Evaluation of interest point detectors. Int J Comput Vis 37:151–172.  https://doi.org/10.1023/A:1008199403446 CrossRefGoogle Scholar
  23. 23.
    Shamloo A (2014) Cell-cell interactions mediate cytoskeleton organization and collective endothelial cell chemotaxis. Cytoskeleton 71:501–512.  https://doi.org/10.1002/cm.21185 CrossRefPubMedGoogle Scholar
  24. 24.
    Suffoletto K, Ye NN, Meng FJ, Verma D, Hua SZ (2015) Intracellular forces during guided cell growth on micropatterns using FRET measurement. J Biomech 48:627–635.  https://doi.org/10.1016/j.jbiomech.2014.12.051 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Tambe DT, Hardin CC, Angelini TE, Rajendran K, Park CY, Serra-Picamal X, Zhou EHH, Zaman MH, Butler JP, Weitz DA, Fredberg JJ, Trepat X (2011) Collective cell guidance by cooperative intercellular forces. Nat Mater 10:469–475.  https://doi.org/10.1038/Nmat3025 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Zhang WJ, Li HQ (2017) Automated segmentation of overlapped nuclei using concave point detection and segment grouping. Pattern Recogn 71:349–360.  https://doi.org/10.1016/j.patcog.2017.06.021 CrossRefGoogle Scholar

Copyright information

© International Federation for Medical and Biological Engineering 2018

Authors and Affiliations

  1. 1.School of Information and ElectronicsBeijing Institute of TechnologyBeijingChina
  2. 2.School of Aerospace EngineeringBeijing Institute of TechnologyBeijingChina
  3. 3.Department of Engineering MechanicsZhejiang UniversityZhejiangChina

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