Mechanical environment plays pivotal roles in regulating stem cell commitment and functions. However, it remains unclear on how mechanical stimuli are transmitted into biochemical signals in stem cells. In this study, we investigated the molecular and biophysical mechanisms by which mechanical forces regulate Ca2+ signaling in human mesenchymal stem cells (HMSCs), integrating genetically encoded Ca2+ biosensor based on fluorescence resonance energy transfer (FRET) and optical laser tweezers. Laser-tweezer-traction of the cell membrane induces intracellular Ca2+ oscillations caused by Ca2+ release from endoplasmic reticulum (ER) in the absence of extracellular Ca2+. These force-induced Ca2+ oscillations produced by ER Ca2+ release are mediated not only by the mechanical support of cytoskeleton and actomyosin contractility, but also by mechanosensitive Ca2+ channels on the plasma membrane, specifically TRPM7. When the ER Ca2+ release is inhibited and the extracellular Ca2+ level is restored, laser-tweezer-traction of the cell can induce the intracellular Ca2+ increase, which is mediated by the cytoskeletal structure but not actomyosin contractility. Taken together, our results indicate that active actomyosin contractility regulated by MLCK and myosin II is essential for the force transmission into the deep intracellular organelles but dispensable for the mechanical regulation of plasma membrane channels.

Distinct mechanisms regulating calcium signals at the plasma membrane and endoplasmic reticulum in response to mechanical stimulation

243rd National Meeting (2012)

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