Viscoelastic properties of human mesenchymally-derived stem cells and primary osteoblasts, chondrocytes, and adipocytes

Abstract

The mechanical properties of single cells play important roles in regulating cell-matrix interactions, potentially influencing the process of mechanotransduction. Recent studies also suggest that cellular mechanical properties may provide novel biological markers, or "biomarkers," of cell phenotype, reflecting specific changes that occur with disease, differentiation, or cellular transformation. Of particular interest in recent years has been the identification of such biomarkers that can be used to determine specific phenotypic characteristics of stem cells that separate them from primary, differentiated cells. The goal of this study was to determine the elastic and viscoelastic properties of three primary cell types of mesenchymal lineage (chondrocytes, osteoblasts, and adipocytes) and to test the hypothesis that primary differentiated cells exhibit distinct mechanical properties compared to adult stem cells (adipose-derived or bone marrow-derived mesenchymal stem cells). In an adherent, spread configuration, chondrocytes, osteoblasts, and adipocytes all exhibited significantly different mechanical properties, with osteoblasts being stiffer than chondrocytes and both being stiffer than adipocytes. Adipose-derived and mesenchymal stem cells exhibited similar properties to each other, but were mechanically distinct from primary cells, particularly when comparing a ratio of elastic to relaxed moduli. These findings will help more accurately model the cellular mechanical environment in mesenchymal tissues, which could assist in describing injury thresholds and disease progression or even determining the influence of mechanical loading for tissue engineering efforts. Furthermore, the identification of mechanical properties distinct to stem cells could result in more successful sorting procedures to enrich multipotent progenitor cell populations.

High-throughput physical phenotyping of cell differentiation

“…Pronounced cell shape changes occur, mediated in part by extensive reorganization of actin into thick bundles at the cell periphery 30,31 . In addition, previous work has also demonstrated that MSCs undergo changes in mechanical properties such as Young's modulus during osteogenesis, although the nature of the change can be method dependent 32,33 . These changes in cell shape due to actin reorganization may help explain the differences in cell morphology observed in m-DC (Figure 2).…”

Mechanisms of osteocyte stimulation in osteoporosis

“…In reality it would be expected that there would indeed be a non-linear relationship between loading and stimulation, due to the complex non-linear material properties of bone matrix and also the time-dependant interstitial fluid flow within the lacunar canalicular network. However, we have assumed linear elastic behaviour for the osteocyte due to its long relaxation time (41.5 s) relative to average frequency of physiological loading (~1 s) (Appelman et al 2011;Darling et al 2008). It should also be noted that the elastic modulus variation study was investigated only using a finite element approach as it is not known how changes in tissue composition could alter the boundary conditions on the fluid flow within the PCM.…”

“…While in vivo loading is of bone is dynamic and cyclic (Fritton et al 2000), we have assumed linear elastic behaviour for the osteocyte due to its long relaxation time (41.5 s) relative to average frequency of physiological loading (~1 s) (Appelman et al 2011;Darling et al 2008), thus allowing simplification of loading to uniaxial ramped static loading. Loading was applied symmetrically, while simultaneously constraining the opposing faces symmetrically to prevent rigid body motion.…”

Nanobiomechanics of living cells: a review

“…Table 8 summarizes the mechanical properties of the different cell types and the change in their morphology. In that case, a borosilicate glass sphere (5 mm diameter) probe was used for the AFM nanoindentation [107].…”