Modulation of cellular mechanics during osteogenic differentiation of human mesenchymal stem cells
Igor Titushkin 1 and Michael Cho 2*
1 University of Illinois at Chicago
2 University of Illinois
* To whom correspondence should be addressed. E-mail: mcho{at}uic.edu.
Submitted on February 28, 2007
Revised on April 23, 2007
Accepted on 13 June 2007
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Abstract |
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Recognition of the growing role of human mesenchymal stem cells (hMSC) in tissue engineering and regenerative medicine requires a thorough understanding of intracellular biochemical and biophysical processes that may direct the cell's commitment to a particular lineage. In this study, we characterized the distinct biomechanical properties of hMSCs, including the average Young's modulus determined with AFM (3.2 ± 1.4 kPa for hMSC vs. 1.7 ± 1.0 kPa for fully differentiated osteoblasts), and the average membrane tether length measured with laser optical tweezers (10.6 ± 1.1 µm for stem cells, and 4.0 ± 1.1 µm for osteoblasts). These differences in the cell elasticity and membrane mechanics result primarily from differential actin cytoskeleton organization in these two cell types, whereas microtubules did not appear to affect the cellular mechanics. The membrane-cytoskeleton linker proteins may contribute to a stronger interaction of the plasma membrane with F-actins and shorter membrane tether length in osteoblasts than in stem cells. Actin depolymerization or ATP depletion caused a 2-3 fold increase in the membrane tether length in osteoblasts, but had essentially no effect on the stem cells membrane tethers. Actin remodeling in the course of a 10-day osteogenic differentiation of hMSC mediates the temporally correlated dynamical changes in the cell elasticity and the membrane mechanics. For example, after a 10-day culture in osteogenic medium, the hMSC mechanical characteristics were comparable to those of mature bone cells. Based on quantitative characterization of the actin cytoskeleton remodeling during osteodifferentiation, we postulate that the actin cytoskeleton play a pivotal role in determining the hMSC mechanical properties and modulation of cellular mechanics at the early stage of stem cell osteodifferentiation.
Key Words:
atomic force microscopy, cellular mechanics, cytoskeleton remodeling, mesenchymal stem cell
