Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-24T20:52:23.889Z Has data issue: false hasContentIssue false
  • English
  • Français

Deformation of the cell nucleus under indentation: Mechanics and mechanisms

Published online by Cambridge University Press:  01 August 2006

A. Vaziri ,
H. Lee  and
M.R. Kaazempur Mofrad
A. Vaziri*
Affiliation:
Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138
H. Lee
Affiliation:
Department of Mechanical Engineering and Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
M.R. Kaazempur Mofrad
Affiliation:
Department of Bioengineering, University of California, Berkeley, California 94720
*
a) Address all correspondence to this author. e-mail: [email protected]
Get access

Abstract

Computational models of the cell nucleus, along with experimental observations, can help in understanding the biomechanics of force-induced nuclear deformation and mechanisms of stress transition throughout the nucleus. Here, we develop a computational model for an isolated nucleus undergoing indentation, which includes separate components representing the nucleoplasm and the nuclear envelope. The nuclear envelope itself is composed of three separate layers: two thin elastic layers representing the inner and outer nuclear membranes and one thicker layer representing the nuclear lamina. The proposed model is capable of separating the structural role of major nuclear components in the force-induced biological response of the nucleus (and ultimately the cell). A systematic analysis is carried out to explore the role of major individual nuclear elements, namely inner and outer membranes, nuclear lamina, and nucleoplasm, as well as the loading and experimental factors such as indentation rate and probe angle, on the biomechanical response of an isolated nucleus in atomic force microscopy indentation experiment.

Keywords

BiologicalNanoscale
Type
Articles
Information
Journal of Materials Research , Volume 21 , Issue 8 , August 2006 , pp. 2126 - 2135
Copyright
Copyright © Materials Research Society 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Aebi, U., Cohn, J., Buhle, L., Gerace, L.: The nuclear lamina is a meshwork of intermediate-type filaments. Nature 323, 560 (1986).Google Scholar
2.Hutchison, C.J.: Lamins: Building blocks or regulators of gene expression? Nat. Rev. Mol. Cell Biol. 3, 848 (2002).Google Scholar
3.Newport, J.W., Forbes, D.J.: The nucleus: Structure, function, and dynamics. Annu. Rev. Biochem. 56, 535 (1987).CrossRefGoogle ScholarPubMed
4.Davies, P.F.: Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75, 519 (1995).Google Scholar
5.Ingber, D.E.: Tensegrity: The architectural basis of cellular mechanotransduction. Annu. Rev. Physiol. 59, 575 (1997).CrossRefGoogle ScholarPubMed
6.Janmey, P.A.: The cytoskeleton and cell signaling: Component localization and mechanical coupling. Physiol. Rev. 78, 763 (1998).CrossRefGoogle ScholarPubMed
7.Dai, G., Kaazempur-Mofrad, N.R., Natarajan, S., Zhang, Y., Vaughn, S., Blackman, B.R., Kamm, R.D., Garcia-Cardena, G., Gimbrone, M.A. Jr.: Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc. Natl. Acad. Sci. USA 101, 14871 (2004).Google Scholar
8.Dahl, K.N., Kahn, S.M., Wilson, K.L., Discher, D.E.: The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber. J. Cell Sci. 117, 4779 (2004).Google Scholar
9.Lammerding, J., Schulze, P.C., Takahashi, T., Kozlov, S., Sullivan, T., Kamm, R.D., Stewart, C.L., Lee, R.T.: Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Invest. 113, 370 (2004).CrossRefGoogle ScholarPubMed
10.Deguchi, S., Maeda, K., Ohashi, T., Sato, M.: Flow-induced hardening of endothelial nucleus as an intracellular stress-bearing organelle. J. Biomech. 38, 1751 (2005).Google Scholar
11.Vaziri, A., Kaazempur-Mofrad, M.R. A computational study on the nuclear mechanics and deformation in micropipette aspiration experiment (2006, unpublished).Google Scholar
12.Guilak, F., Tedrow, J.R., Burgkart, R.: Viscoelastic properties of the cell nucleus. Biochem. Biophys. Res. Commun. 269, 781 (2000).Google Scholar
13.Lemoine, P., McLaughlin, J.M.: Nanomechanical measurements on polymers using contact mode atomic force microscopy. Thin Solid Films 339, 258 (1999).Google Scholar
14.Magonov, S.N., Reneker, D.H.: Characterization of polymer surfaces with atomic force microscopy. Annu. Rev. Mater. Sci. 27, 175 (1997).CrossRefGoogle Scholar
15.VanLandingham, M.R., Dagastine, R.R., Eduljee, R.F., McCullough, R.L., Gillespie, J.W.: Characterization of nanoscale property variations in polymer composite systems: 1. Experimental results. Composites A 30, 75 (1999).CrossRefGoogle Scholar
16.Shulha, H., Kovalev, A., Myshkin, N., Tsukruk, V.V.: Some aspects of AFM nanomechanical probing of surface polymer films. Eur. Polym. J. 40, 949 (2004).CrossRefGoogle Scholar
17.Efimenko, K., Rackaitis, M., Manias, W., Vaziri, A., Mahadevan, L., Genzer, J.: Nested self-similar wrinkling patterns in skins. Nat. Mater. 4, 293 (2005).CrossRefGoogle ScholarPubMed
18.Domke, J., Radmacher, M.: Measuring the elastic properties of thin polymeric films with the atomic force microscope. Langmuir 14, 3320 (1998).Google Scholar
19.McGuiggan, P.M., Yarusso, D.J.: Measurement of the loss tangent of a thin polymeric films using the atomic force microscopy. J. Mater. Res. 19, 387 (2004).CrossRefGoogle Scholar
20.Lim, Y.Y., Chaudhri, M.M., Enomoto, Y.: Accurate determination of the mechanical properties of thin aluminum films deposited on sapphire flats using nanoindentations. J. Mater. Res. 14, 2314 (1999).CrossRefGoogle Scholar
21.Bezanilla, M., Drake, B., Nudler, E., Kashlev, M., Hansma, P.K., Hansma, H.G.: Motion and enzymatic degradation of DNA in the atomic force microscope. Biophys. J. 67, 2454 (1994).Google Scholar
22.Hoh, J.H., Schoenenberger, C.A.: Surface morphology and mechanical properties of MDCK monolayers by atomic force microscopy. J. Cell Sci. 107, 1105 (1994).Google Scholar
23.Mahaffy, R.E., Shih, C.K., MacKintosh, F.C., Kas, J.: Scanning probe-based frequency-dependent microrheology of polymer gels and biological cells. Phys. Rev. Lett. 85, 880 (2000).CrossRefGoogle ScholarPubMed
24.Radmacher, M., Fritz, M., Kacher, C.M., Cleveland, J.P., Hansma, P.K.: Measuring the viscoelastic properties of human platelets with the atomic force microscope. Biophys. J. 70, 556 (1996).Google Scholar
25.Caille, N., Thoumine, O., Tardy, Y., Meister, J.J.: Contribution of the nucleus to the mechanical properties of endothelial cells. J. Biomech. 35, 177 (2002).Google Scholar
26.Dahl, K.N., Engler, A.J., Pajerowski, J.D., Discher, D.E. Power-law rheology of isolated nuclei with deformation mapping of nuclear sub-structures. Biophys. J. (2005).Google Scholar
27.Tseng, Y., Lee, J.S., Kole, T.P., Jiang, I., Wirtz, D.: Micro-organization and visco-elasticity of the interphase nucleus revealed by particle nanotracking. J. Cell Sci. 117, 2159 (2004).Google Scholar
28.Senda, T., Iizuka-Kogo, A., Shimomura, A.: Visualization of the nuclear lamina in mouse anterior pituitary cells and immunocytochemical detection of lamin A/C by quick-freeze freeze-substitution electron microscopy. J. Histochem. Cytochem. 53, 497 (2005).Google Scholar
29.Schatten, G., Thoman, M.: Nuclear surface complex as observed with the high resolution scanning electron microscope. Visualization of the membrane surfaces of the neclear envelope and the nuclear cortex from Xenopus laevis oocytes. J. Cell Biol. 77, 517 (1978).Google Scholar
30.Burke, B., Stewart, C.L.: Life at the edge: The nuclear envelope and human disease. Nat. Rev. Mol. Cell Biol. 3, 575 (2002).CrossRefGoogle ScholarPubMed
31.Maraldi, N.M., Lattanzi, G., Marmiroli, S., Squarzoni, S., Manzoli, F.A.: New roles for lamins, nuclear envelope proteins and actin in the nucleus. Adv. Enzyme Regul. 44, 155 (2004).CrossRefGoogle ScholarPubMed
32.Ostlund, C., Worman, H.J.: Nuclear envelope proteins and neuromuscular diseases. Muscle Nerve 27, 393 (2003).Google Scholar
33.Karcher, H., Lammerding, J., Huang, H., Lee, R.T., Kamm, R.D., Kaazempur-Mofrad, M.R.: A three-dimensional viscoelastic model for cell deformation with experimental verification. Biophys. J. 85, 3336 (2003).Google Scholar
34.Mohandas, N., Evans, E.: Mechanical properties of the red cell membrane in relation to molecular structure and genetic defects. Annu. Rev. Biophys. Biomol. Struct. 23, 787 (1994).CrossRefGoogle ScholarPubMed
35.Thoumine, O., Ott, A., Cardoso, O., Meister, J.J.: Microplates: A new tool for manipulation and mechanical perturbation of individual cells. J. Biochem. Biophys. Methods 39, 47 (1999).Google Scholar
36.Bilodeau, G.G.: Regular pyramid punch problem. J. Appl. Mech. Trans. ASME 59, 519 (1992).Google Scholar
37.Hertz, H.: On the contact of solid flexible bodies. J. reine angewandte Math. 92, 156 (1881).Google Scholar
38.Zhelev, D.V., Needham, D., Hochmuth, R.M.: Role of the membrane cortex in neutrophil deformation in small pipets. Biophys. J. 67, 696 (1994).Google Scholar
39.Mahaffy, R.E., Park, S., Gerde, E., Kas, J., Shih, C.K.: Quantitative analysis of the viscoelastic properties of thin regions of fibroblasts using atomic force microscopy. Biophys. J. 86, 1777 (2004).Google Scholar
40.Hategan, A., Law, R., Kahn, S., Discher, D.E.: Adhesively-tensed cell membranes: Lysis kinetics and atomic force microscopy probing. Biophys. J. 85, 2746 (2003).Google Scholar