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Elife. 2015 Feb 10;4:e04876. doi: 10.7554/eLife.04876.

Distinct mechanisms regulating mechanical force-induced Ca²⁺ signals at the plasma membrane and the ER in human MSCs.

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Neuroscience Program, University of Illinois, Urbana-Champaign, Urbana, United States.
Department of Physics, University of Illinois, Urbana-Champaign, Urbana, United States.
Department of Biomedical Engineering, Beckman Laser Institute, University of California, Irvine, Irvine, United States.
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Boulder, United States.
Department of Mechanical Science and Engineering, University of Illinois, Urbana-Champaign, Urbana, United States.
Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, United States.


It is unclear that how subcellular organelles respond to external mechanical stimuli. Here, we investigated the molecular mechanisms by which mechanical force regulates Ca(2+) signaling at endoplasmic reticulum (ER) in human mesenchymal stem cells. Without extracellular Ca(2+), ER Ca(2+) release is the source of intracellular Ca(2+) oscillations induced by laser-tweezer-traction at the plasma membrane, providing a model to study how mechanical stimuli can be transmitted deep inside the cell body. This ER Ca(2+) release upon mechanical stimulation is mediated not only by the mechanical support of cytoskeleton and actomyosin contractility, but also by mechanosensitive Ca(2+) permeable channels on the plasma membrane, specifically TRPM7. However, Ca(2+) influx at the plasma membrane via mechanosensitive Ca(2+) permeable channels is only mediated by the passive cytoskeletal structure but not active actomyosin contractility. Thus, active actomyosin contractility is essential for the response of ER to the external mechanical stimuli, distinct from the mechanical regulation at the plasma membrane.


FRET biosensor; biophysics; calcium signals; developmental biology; mechanical stimulation; mesenchymal stem cells; molecular imaging; none; optical laser tweezers; stem cells; structural biology

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