title: Prolonged mechanical stretch initiates intracellular calcium oscillations in human mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) are a promising candidate for cell-based therapy in regenerative medicine. These stem cells can interact with their mechanical microenvironment to control their functions. External mechanical cues can be perceived and transmitted into intracellular calcium dynamics to regulate various cellular processes. Recent studies indicate that human MSCs (hMSCs) exhibit a heterogeneous nature with a subset of hMSCs lacking spontaneous calcium oscillations. In this study, we studied whether and how external mechanical tension can be applied to trigger and restore the intracellular calcium oscillation in these hMSCs lacking spontaneous activities. Utilizing the fluorescence resonance energy transfer (FRET) based calcium biosensor, we found that this subpopulation of hMSCs can respond to a prolonged mechanical stretch (PMS). Further results revealed that the triggering of calcium oscillations in these cells is dependent on the calcium influx across the plasma membrane, as well as on both cytoskeletal supports, myosin light chain kinase (MLCK)-driven actomyosin contractility, and phospholipase C (PLC) activity. Thus, our report confirmed that mechanical tension can govern the intracellular calcium oscillation in hMSCs, possibly via the control of the calcium permeability of channels at the plasma membrane. Our results also provide novel mechanistic insights into how hMSCs sense mechanical environment to regulate cellular functions.
authors.affiliation: Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; Department of Bioengineering and Institute of Engineering in Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Lu
authors.affiliation: Institute of Mechanobiology and Medical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Ying-Xin
authors.initials: YX
authors.lastname: Qi
authors.affiliation: Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; Department of Bioengineering and Institute of Engineering in Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Yingxiao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D001696:Biomechanical Phenomena; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism*; D055595:Mechanical Phenomena; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010539:Permeability; D013314:Stress, Mechanical; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D015544:Inositol 1,4,5-Trisphosphate; D000205:Actomyosin; D010738:Type C Phospholipases