Skip to main content
SpringerLink
Log in

Deformability of Human Mesenchymal Stem Cells Is Dependent on Vimentin Intermediate Filaments

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

A Correction to this article was published on 02 January 2018

This article has been updated

Abstract

Mesenchymal stem cells (MSCs) are being studied extensively due to their potential as a therapeutic cell source for many load-bearing tissues. Compression of tissues and the subsequent deformation of cells are just one type physical strain MSCs will need to withstand in vivo. Mechanotransduction by MSCs and their mechanical properties are partially controlled by the cytoskeleton, including vimentin intermediate filaments (IFs). Vimentin IF deficiency has been tied to changes in mechanosensing and mechanical properties of cells in some cell types. However, how vimentin IFs contribute to MSC deformability has not been comprehensively studied. Investigating the role of vimentin IFs in MSC mechanosensing and mechanical properties will assist in functional understanding and development of MSC therapies. In this study, we examined vimentin IFs’ contribution to MSCs’ ability to deform under external deformation using RNA interference. Our results indicate that a deficient vimentin IF network decreases the deformability of MSCs, and that this may be caused by the remaining cytoskeletal network compensating for the vimentin IF network alteration. Our observations introduce another piece of information regarding how vimentin IFs are involved in the complex role the cytoskeleton plays in the mechanical properties of cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

Change history

  • 02 January 2018

    This erratum is to correct the following: (1) in the Western Blotting subsection under the Materials and Methods section, the concentration of protein from each sample loaded into Criterion Tris–HCl gels was incorrectly stated as 155 µg of protein. The correct value is 9.7 µg; (2) in Fig. 1b, the bar graph showed incorrect values for semi-quantitation of Western blots. Figure 1 has been updated with a corrected graph in Fig. 1b only.

References

  1. Afizah, H., and J. H. P. Hui. Mesenchymal stem cell therapy for osteoarthritis. J. Clin. Orthop. Trauma 7:177–182, 2016.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Broom, N. D., and D. B. Myers. A study of the structural response of wet hyaline cartilage to various loading situations. Connect. Tissue Res. 7:227–237, 1980.

    Article  CAS  PubMed  Google Scholar 

  3. Brown, M. J., J. A. Hallam, E. Colucci-Guyon, and S. Shaw. Rigidity of circulating lymphocytes is primarily conferred by vimentin intermediate filaments. J. Immunol. 166:6640–6646, 2001.

    Article  CAS  PubMed  Google Scholar 

  4. Capín-Gutiérrez, N., P. Talamás-Rohana, A. González-Robles, C. Lavalle-Montalvo, and J. B. Kourí. Cytoskeleton disruption in chondrocytes from a rat osteoarthrosic (OA)-induced model: its potential role in OA pathogenesis. Histol. Histopathol. 19:1125–1132, 2004.

    PubMed  Google Scholar 

  5. Chahine, N. O., C. Blanchette, C. B. Thomas, J. Lu, D. Haudenschild, and G. G. Loots. Effect of age and cytoskeletal elements on the indentation-dependent mechanical properties of chondrocytes. PLoS ONE 8:e61651, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen, Q., B. Suki, and K.-N. An. Dynamic mechanical properties of agarose gels modeled by a fractional derivative model. J. Biomech. Eng. 126:666–671, 2004.

    Article  PubMed  Google Scholar 

  7. Eckes, B., D. Dogic, E. Colucci-Guyon, N. Wang, A. Maniotis, D. Ingber, A. Merckling, F. Langa, M. Aumailley, A. Delouvée, et al. Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts. J. Cell Sci. 111:1897–1907, 1998.

    CAS  PubMed  Google Scholar 

  8. Fukui, N., C. R. Purple, and L. J. Sandell. Cell biology of osteoarthritis: the chondrocyte’s response to injury. Curr. Rheumatol. Rep. 3:496–505, 2001.

    Article  CAS  PubMed  Google Scholar 

  9. Gladilin, E., P. Gonzalez, and R. Eils. Dissecting the contribution of actin and vimentin intermediate filaments to mechanical phenotype of suspended cells using high-throughput deformability measurements and computational modeling. J. Biomech. 47:2598–2605, 2014.

    Article  PubMed  Google Scholar 

  10. González-Cruz, R. D., V. C. Fonseca, and E. M. Darling. Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells. Proc. Natl. Acad. Sci. USA 109:E1523–E1529, 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Guilak, F. Biomechanical factors in osteoarthritis. Best Pract. Res. Clin. Rheumatol. 25:815–823, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Guilak, F., A. Ratcliffe, and V. C. Mow. Chondrocyte deformation and local tissue strain in articular cartilage: a confocal microscopy study. J. Orthop. Res. 13:410–421, 1995.

    Article  CAS  PubMed  Google Scholar 

  13. Guo, M., A. J. Ehrlicher, S. Mahammad, H. Fabich, M. H. Jensen, J. R. Moore, J. J. Fredberg, R. D. Goldman, and D. A. Weitz. The role of vimentin intermediate filaments in cortical and cytoplasmic mechanics. Biophys. J. 105:1562–1568, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Haudenschild, D. R., J. Chen, N. Pang, N. Steklov, S. P. Grogan, M. K. Lotz, and D. D. D’Lima. Vimentin contributes to changes in chondrocyte stiffness in osteoarthritis. J. Orthop. Res. 29:20–25, 2011.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jo, C. H., Y. G. Lee, W. H. Shin, H. Kim, J. W. Chai, E. C. Jeong, J. E. Kim, H. Shim, J. S. Shin, I. S. Shin, J. C. Ra, S. Oh, and K. S. Yoon. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells 32:1254–1266, 2014.

    Article  CAS  PubMed  Google Scholar 

  16. Lambrecht, S., G. Verbruggen, P. C. M. Verdonk, D. Elewaut, and D. Deforce. Differential proteome analysis of normal and osteoarthritic chondrocytes reveals distortion of vimentin network in osteoarthritis. Osteoarthritis Cartilage 16:163–173, 2008.

    Article  CAS  PubMed  Google Scholar 

  17. Lee, D. A., and D. L. Bader. The development and characterization of an in vitro system to study strain-induced cell deformation in isolated chondrocytes. Vitro Cell. Dev. Biol. Anim. 31:828–835, 1995.

    Article  CAS  Google Scholar 

  18. Lee, D. A., M. M. Knight, J. F. Bolton, B. D. Idowu, M. V. Kayser, and D. L. Bader. Chondrocyte deformation within compressed agarose constructs at the cellular and sub-cellular levels. J. Biomech. 33:81–95, 2000.

    Article  CAS  PubMed  Google Scholar 

  19. Lee, J.-H., H.-K. Park, and K. S. Kim. Intrinsic and extrinsic mechanical properties related to the differentiation of mesenchymal stem cells. Biochem. Biophys. Res. Commun. 473:752–757, 2016.

    Article  CAS  PubMed  Google Scholar 

  20. Mathieu, P. S., and E. G. Loboa. Cytoskeletal and focal adhesion influences on mesenchymal stem cell shape, mechanical properties, and differentiation down osteogenic, adipogenic, and chondrogenic pathways. Tissue Eng. Part B Rev. 18:436–444, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mauck, R. L., B. A. Byers, X. Yuan, and R. S. Tuan. Regulation of cartilaginous ECM gene transcription by chondrocytes and MSCs in 3D culture in response to dynamic loading. Biomech. Model. Mechanobiol. 6:113–125, 2006.

    Article  PubMed  Google Scholar 

  22. McCloy, R. A., S. Rogers, C. E. Caldon, T. Lorca, A. Castro, and A. Burgess. Partial inhibition of Cdk1 in G2 phase overrides the SAC and decouples mitotic events. Cell Cycle 13:1400–1412, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ofek, G., D. C. Wiltz, and K. A. Athanasiou. Contribution of the cytoskeleton to the compressive properties and recovery behavior of single cells. Biophys. J. 97:1873–1882, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pan, W., E. Petersen, N. Cai, G. Ma, J. R. Lee, Z. Feng, K. Liao, and K. W. Leong. Viscoelastic properties of human mesenchymal stem cells, 2005. doi:10.1109/IEMBS.2005.1615559.

  25. Plodinec, M., M. Loparic, R. Suetterlin, H. Herrmann, U. Aebi, and C.-A. Schoenenberger. The nanomechanical properties of rat fibroblasts are modulated by interfering with the vimentin intermediate filament system. J. Struct. Biol. 174:476–484, 2011.

    Article  CAS  PubMed  Google Scholar 

  26. Rathje, L.-S. Z., N. Nordgren, T. Pettersson, D. Rönnlund, J. Widengren, P. Aspenström, and A. K. B. Gad. Oncogenes induce a vimentin filament collapse mediated by HDAC6 that is linked to cell stiffness. Proc. Natl. Acad. Sci. USA 111:1515–1520, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rollín, R., F. Marco, E. Camafeita, E. Calvo, L. López-Durán, J. Á. Jover, J. A. López, and B. Fernández-Gutiérrez. Differential proteome of bone marrow mesenchymal stem cells from osteoarthritis patients. Osteoarthr. Cartil. 16:929–935, 2008.

    Article  PubMed  Google Scholar 

  28. Steward, A. J., D. R. Wagner, and D. J. Kelly. The pericellular environment regulates cytoskeletal development and the differentiation of mesenchymal stem cells and determines their response to hydrostatic pressure. Eur. Cell Mater. 25:167–178, 2013.

    Article  CAS  PubMed  Google Scholar 

  29. Titushkin, I. A., and M. R. Cho. Controlling cellular biomechanics of human mesenchymal stem cells, 2009. doi:10.1109/IEMBS.2009.5333949.

  30. Trickey, W. R., T. P. Vail, and F. Guilak. The role of the cytoskeleton in the viscoelastic properties of human articular chondrocytes. J. Orthop. Res. Off. Publ. Orthop. Res. Soc. 22:131–139, 2004.

    Article  Google Scholar 

  31. Twomey, J. D., P. I. Thakore, D. A. Hartman, E. G. H. Myers, and A. H. Hsieh. Roles of type VI collagen and decorin in human mesenchymal stem cell biophysics during chondrogenic differentiation. Eur. Cell. Mater. 27:237–250, 2014.

    Article  CAS  PubMed  Google Scholar 

  32. Urban, J. P. The chondrocyte: a cell under pressure. Br. J. Rheumatol. 33:901–908, 1994.

    Article  CAS  PubMed  Google Scholar 

  33. Vigfúsdóttir, Á. T., C. Pasrija, P. I. Thakore, R. B. Schmidt, and A. H. Hsieh. Role of pericellular matrix in mesenchymal stem cell deformation during chondrogenic differentiation. Cell. Mol. Bioeng. 3:387–397, 2010.

    Article  Google Scholar 

  34. Wang, N., and D. Stamenović. Contribution of intermediate filaments to cell stiffness, stiffening, and growth. Am. J. Physiol. Cell Physiol. C279:C188–194, 2000.

    Article  Google Scholar 

  35. Wu, J. Z., W. Herzog, and M. Epstein. Modelling of location- and time-dependent deformation of chondrocytes during cartilage loading. J. Biomech. 32:563–572, 1999.

    Article  CAS  PubMed  Google Scholar 

  36. Yourek, G., M. A. Hussain, and J. J. Mao. Cytoskeletal changes of mesenchymal stem cells during differentiation. ASAIO J. (Am. Soc. Artif. Intern. Organs 1992) 53:219–228, 2007.

    Article  Google Scholar 

  37. Yu, H., C. Y. Tay, W. S. Leong, S. C. W. Tan, K. Liao, and L. P. Tan. Mechanical behavior of human mesenchymal stem cells during adipogenic and osteogenic differentiation. Biochem. Biophys. Res. Commun. 393:150–155, 2010.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Science Foundation (CMMI 1563721, DRW; CBET 0845754, AHH).

Conflict of interest

No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Author information

Authors and Affiliations

  1. Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA

    Poonam Sharma, Zachary T. Bolten & Adam H. Hsieh

  2. Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA

    Diane R. Wagner

  3. Department of Orthopaedics, University of Maryland, Baltimore, MD, USA

    Adam H. Hsieh

Authors
  1. Poonam Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zachary T. Bolten
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Diane R. Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adam H. Hsieh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adam H. Hsieh.

Additional information

Associate Editor Eric M. Darling oversaw the review of this article.

A correction to this article is available online at https://doi.org/10.1007/s10439-017-1975-5.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sharma, P., Bolten, Z.T., Wagner, D.R. et al. Deformability of Human Mesenchymal Stem Cells Is Dependent on Vimentin Intermediate Filaments. Ann Biomed Eng 45, 1365–1374 (2017). https://doi.org/10.1007/s10439-016-1787-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-016-1787-z

Keywords

Search

Navigation