Dynamic Force Generation by Neural Stem Cells
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Mechanical cues may have important roles in tissue morphogenesis; progression through complex functions like differentiation may be associated with changes in cellular force generation and mechanosensing. To explore this concept, we use elastomer pillar arrays to map forces generated by neural stem cells in vitro, and identify two distinct dynamics of force generation. First, cell generated forces decrease as cells transition from a proliferative mode to differentiation, a process covering several days. This change in force generation correlates with a loss of sensitivity to substrate rigidity over a series of polydimethylsiloxane substrates. Second, neural stem cells exhibit a faster pattern of localized contractions at the cell body and outlying processes; each lasts on the order of minutes, and is not synchronized across the cell. This faster process is reminiscent of migratory behavior observed in vivo, and may be involved in controlling the motion of internal structures such as the cell nucleus. These results together provide new clues into the role of forces during development, and may lead to design principles for materials targeted for use in the central nervous system.
KeywordsCellular traction force Stem cell Microenvironment Differentiation Proliferation
This work was funded by the National Institutes of Health through the NIH Roadmap for Medical Research (PN2 EY016586).
Application of blebbstatin to cells in expansion media induces rapid changes in morphology. Corresponding effects on nuclear migration are quantified in Fig. 5D, E (AVI 3787 kb)
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