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First published online 29 January 2008
doi: 10.1242/jcs.022053

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Actin stress fibers transmit and focus force to activate mechanosensitive channels

¹ Cell Mechano-sensing Project ICORP/SORST, Japan Science and Technology Agency, Nagoya University Graduate School of Medicine, 65 Tsurumai Syouwa-ku, Nagoya 468-8550, Japan
² Department of Physiology, Nagoya University Graduate School of Medicine, 65 Tsurumai Syouwa-ku, Nagoya 468-8550, Japan
³ Department of Molecular Physiology, National Institute for Physiological Sciences, NINS, Myodaiji, Okazaki 444-8585, Japan

^* Author for correspondence (e-mail: msokabe{at}med.nagoya-u.ac.jp)

Accepted 19 November 2007

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 Ca²⁺ 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.

Key words: Actin, Mechanosensitive channel, Mechanical stress, Stress fiber