Annals of Biomedical Engineering

, Volume 45, Issue 5, pp 1365–1374 | Cite as

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

  • Poonam Sharma
  • Zachary T. Bolten
  • Diane R. Wagner
  • Adam H. Hsieh
Article

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.

Keywords

Cytoskeleton Cell deformation RNA interference Mechanotransduction 

References

  1. 1.
    Afizah, H., and J. H. P. Hui. Mesenchymal stem cell therapy for osteoarthritis. J. Clin. Orthop. Trauma 7:177–182, 2016.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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.PubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Guilak, F. Biomechanical factors in osteoarthritis. Best Pract. Res. Clin. Rheumatol. 25:815–823, 2011.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 29.
    Titushkin, I. A., and M. R. Cho. Controlling cellular biomechanics of human mesenchymal stem cells, 2009. doi:10.1109/IEMBS.2009.5333949.
  30. 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.CrossRefGoogle Scholar
  31. 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.CrossRefPubMedGoogle Scholar
  32. 32.
    Urban, J. P. The chondrocyte: a cell under pressure. Br. J. Rheumatol. 33:901–908, 1994.CrossRefPubMedGoogle Scholar
  33. 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.CrossRefGoogle Scholar
  34. 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.Google Scholar
  35. 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.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2017

Authors and Affiliations

  • Poonam Sharma
    • 1
  • Zachary T. Bolten
    • 1
  • Diane R. Wagner
    • 2
  • Adam H. Hsieh
    • 1
    • 3
  1. 1.Fischell Department of BioengineeringUniversity of MarylandCollege ParkUSA
  2. 2.Indiana University-Purdue University IndianapolisIndianapolisUSA
  3. 3.Department of OrthopaedicsUniversity of MarylandBaltimoreUSA

Personalised recommendations