title: Actin stress fibers transmit and focus force to activate mechanosensitive channels.
abstract: Mechanosensitive (MS) channels are expressed in various cells in a wide range of phylogenetic lineages from bacteria to humans. Understanding the molecular and biophysical mechanisms of their activation is an important research pursuit. It is controversial whether eukaryotic MS channels need accessory proteins -- typically cytoskeletal structures -- for activation, because MS channel activities are modulated by pharmacological treatments that affect the cytoskeleton. Here we demonstrate that direct mechanical stimulation (stretching) of an actin stress fiber using optical tweezers can activate MS channels in cultured human umbilical vein endothelial cells (HUVECs). Furthermore, by using high-speed total internal reflection microscopy, we visualized spots of Ca(2+) influx across individual MS channels distributed near focal adhesions in the basal surface of HUVECs. This study provides the first direct evidence that the cytoskeleton works as a force-transmitting and force-focusing molecular device to activate MS channels in eukaryotic cells.
authors.affiliation: Cell Mechano-sensing Project ICORP/SORST, Japan Science and Technology Agency, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kimihide
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tatsumi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sokabe
mesh_terms: D000199:Actins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D040542:Mechanotransduction, Cellular; D008856:Microscopy, Fluorescence; D018408:Patch-Clamp Techniques; D022502:Stress Fibers / Q000378:metabolism*; D013314:Stress, Mechanical; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D000199:Actins; D007473:Ion Channels; D002118:Calcium