title: Distinct mechanisms regulating mechanical force-induced Ca²⁺ signals at the plasma membrane and the ER in human MSCs.
abstract: 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.
authors: Neuroscience Program, University of Illinois, Urbana-Champaign, Urbana, United States.
authors: Tae-Jin
authors: TJ
authors: Kim
authors: Department of Physics, University of Illinois, Urbana-Champaign, Urbana, United States.
authors: Chirlmin
authors: C
authors: Joo
authors: Neuroscience Program, University of Illinois, Urbana-Champaign, Urbana, United States.
authors: Jihye
authors: J
authors: Seong
authors: Department of Physics, University of Illinois, Urbana-Champaign, Urbana, United States.
authors: Reza
authors: R
authors: Vafabakhsh
authors: Department of Biomedical Engineering, Beckman Laser Institute, University of California, Irvine, Irvine, United States.
authors: Elliot L
authors: EL
authors: Botvinick
authors: Department of Biomedical Engineering, Beckman Laser Institute, University of California, Irvine, Irvine, United States.
authors: Michael W
authors: MW
authors: Berns
authors: Department of Chemistry and Biochemistry, University of Colorado, Boulder, Boulder, United States.
authors: Amy E
authors: AE
authors: Palmer
authors: Department of Mechanical Science and Engineering, University of Illinois, Urbana-Champaign, Urbana, United States.
authors: Ning
authors: N
authors: Wang
authors: Department of Physics, University of Illinois, Urbana-Champaign, Urbana, United States.
authors: Taekjip
authors: T
authors: Ha
authors: Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, United States.
authors: Eric
authors: E
authors: Jakobsson
authors: Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, United States.
authors: Jie
authors: J
authors: Sun
authors: Neuroscience Program, University of Illinois, Urbana-Champaign, Urbana, United States.
authors: Yingxiao
authors: Y
authors: Wang
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D015374:Biosensing Techniques; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D013314:Stress, Mechanical; D014162:Transfection
chemical_list: D000205:Actomyosin; D002118:Calcium
keywords: FRET biosensor; biophysics; calcium signals; developmental biology; mechanical stimulation; mesenchymal stem cells; molecular imaging; none; optical laser tweezers; stem cells; structural biology