Mechanical behavior of human mesenchymal stem cells during adipogenic and osteogenic differentiation.

Human mesenchymal stem cells (hMSCs) have gained widespread attention in the field of tissue engineering but not much is known about the changes of mechanical properties during the process of cell lineage commitment and the mechanisms of these behaviors. It is believed that exploring the inter-relations between stem cells mechanical properties and lineage commitment will shed light on the mechanobiology aspect of differentiation. hMSCs were cultured in adipogenic and osteogenic mediums and the elastic moduli were monitored using micropipette aspiration. It was found that hMSCs undergoing osteogenesis have an instantaneous Young's modulus of 890 +/- 219 Pa and an equilibrium Young's modulus of 224 +/- 40 Pa, each is about 2-fold higher than the control group. Interestingly, cells cultured in adipogenic medium exhibited a slight increase in the cellular modulus followed by a decrease relative to that of the control group. Gene expression study was employed to gain insights into this phenomenon. Concomitant up regulation of actin binding filamin A (FLNa) and gamma-Tubulin with the cellular elastic modulus indicated their important role in mechanical regulation during hMSCs differentiation. Statistical results showed that cell shape and cell area changed with cellular mechanical properties, which means that cell morphology has a close relation with cell elastic modulus in the initial stage of differentiation. Collectively, these results provide a quantitative description of hMSCs mechanical behavior during the process of differentiation as well as the possible accompanying mechanism at the biomolecular level.

[1]  Farshid Guilak,et al.  Viscoelastic properties of human mesenchymally-derived stem cells and primary osteoblasts, chondrocytes, and adipocytes. , 2008, Journal of biomechanics.

[2]  Mauricio González,et al.  Cytoskeletal organization of human mesenchymal stem cells (MSC) changes during their osteogenic differentiation , 2004, Journal of cellular biochemistry.

[3]  I. Titushkin,et al.  Modulation of cellular mechanics during osteogenic differentiation of human mesenchymal stem cells. , 2007, Biophysical journal.

[4]  D. Ingber,et al.  Mechanical behavior in living cells consistent with the tensegrity model , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R M Nerem,et al.  The application of a homogeneous half-space model in the analysis of endothelial cell micropipette measurements. , 1988, Journal of biomechanical engineering.

[6]  K Weber,et al.  Intermediate filaments: structure, dynamics, function, and disease. , 1994, Annual review of biochemistry.

[7]  A. Woods,et al.  Cytoskeleton changes in fibroblast adhesion and detachment. , 1980, Journal of cell science.

[8]  P. Steinert,et al.  The function of intermediate filaments in cell shape and cytoskeletal integrity , 1996, The Journal of cell biology.

[9]  W. R. Jones,et al.  Alterations in the Young's modulus and volumetric properties of chondrocytes isolated from normal and osteoarthritic human cartilage. , 1999, Journal of biomechanics.

[10]  Say Chye Joachim Loo,et al.  Cellular behavior of human mesenchymal stem cells cultured on single-walled carbon nanotube film , 2010 .

[11]  Christopher S. Chen,et al.  Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. , 2004, Developmental cell.

[12]  B. Seed,et al.  A PCR primer bank for quantitative gene expression analysis. , 2003, Nucleic acids research.

[13]  Majd Zayzafoon,et al.  RhoA and Cytoskeletal Disruption Mediate Reduced Osteoblastogenesis and Enhanced Adipogenesis of Human Mesenchymal Stem Cells in Modeled Microgravity , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[14]  Jean-Jacques Meister,et al.  Changes in the mechanical properties of fibroblasts during spreading: a micromanipulation study , 1999, European Biophysics Journal.

[15]  R M Nerem,et al.  Viscoelastic properties of cultured porcine aortic endothelial cells exposed to shear stress. , 1996, Journal of biomechanics.

[16]  R. Reger,et al.  Differentiation and characterization of human MSCs. , 2008, Methods in molecular biology.

[17]  S. Suresh,et al.  Cell and molecular mechanics of biological materials , 2003, Nature materials.

[18]  D. Ingber,et al.  Cellular mechanotransduction: putting all the pieces together again , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  P. Janmey,et al.  The Role of Actin-binding Protein 280 in Integrin-dependent Mechanoprotection* , 1998, The Journal of Biological Chemistry.

[20]  T. Laursen,et al.  Determination of the Poisson's ratio of the cell: recovery properties of chondrocytes after release from complete micropipette aspiration. , 2006, Journal of biomechanics.

[21]  Farshid Guilak,et al.  A thin-layer model for viscoelastic, stress-relaxation testing of cells using atomic force microscopy: do cell properties reflect metastatic potential? , 2007, Biophysical journal.

[22]  Donald E Ingber,et al.  Mechanobiology and diseases of mechanotransduction , 2003, Annals of medicine.

[23]  Johanna Ivaska,et al.  Novel functions of vimentin in cell adhesion, migration, and signaling. , 2007, Experimental cell research.

[24]  H. Joshi,et al.  gamma-tubulin is a minus end-specific microtubule binding protein , 1995, The Journal of cell biology.

[25]  P. Janmey,et al.  HIV infection changes glomerular podocyte cytoskeletal composition and results in distinct cellular mechanical properties. , 2007, American journal of physiology. Renal physiology.

[26]  Kam W Leong,et al.  Viscoelastic behaviour of human mesenchymal stem cells , 2008, BMC Cell Biology.

[27]  Yixian Zheng,et al.  γ-Tubulin is present in Drosophila melanogaster and homo sapiens and is associated with the centrosome , 1991, Cell.

[28]  Viscoelastic Properties of Human Mesenchymal Stem Cells , 2005, 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference.