TitleMechanical stiffness as an improved single-cell indicator of osteoblastic human mesenchymal stem cell differentiation.
Publication TypeJournal Article
Year of Publication2014
AuthorsBongiorno, T, Kazlow, J, Mezencev, R, Griffiths, S, Olivares-Navarrete, R, McDonald, JF, Schwartz, Z, Boyan, BD, McDevitt, TC, Sulchek, T
JournalJournal of Biomechanics
Date PublishedJune 2014
KeywordsBiological Markers, Cell Differentiation, Cells, Cultured, Elastic Modulus, Humans, Integrin-Binding Sialoprotein, Mesenchymal Stromal Cells, Microscopy, Atomic Force, Osteoblasts, Osteocalcin, Osteogenesis, Stem Cells, Tissue Engineering

Although it has been established that cellular stiffness can change as a stem cell differentiates, the precise relationship between cell mechanics and other phenotypic properties remains unclear. Inherent cell heterogeneity and asynchronous differentiation complicate population analysis; therefore, single-cell analysis was employed to determine how changes in cell stiffness correlate with changes in molecular biomarkers during differentiation. Design of a custom gridded tissue culture dish facilitated single-cell comparisons between cell mechanics and other differentiation biomarkers by enabling sequential measurement of cell mechanics and protein biomarker expression at the single cell level. The Young's modulus of mesenchymal stem cells was shown not only to decrease during chemically-induced osteoblast differentiation, but also to correlate more closely with the day of differentiation than did the relative expression of the traditional osteoblast differentiation markers, bone sialoprotein and osteocalcin. Therefore, cell stiffness, a measurable property of individual cells, may serve as an improved indicator of single-cell osteoblast differentiation compared to traditional biological markers. Revelation of additional osteoblast differentiation indicators, such as cell stiffness, can improve identification and collection of starting cell populations, with applications to mesenchymal stem cell therapies and stem cell-based tissue engineering.

Alternate JournalJ Biomech
PubMed ID24296276
PubMed Central IDPMC4024369
Grant ListT32 GM008433 / GM / NIGMS NIH HHS / United States
R01 AR052102 / AR / NIAMS NIH HHS / United States
P40RR017447 / RR / NCRR NIH HHS / United States