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Estimating the Sensitivity of Mechanosensitive Ion Channels to Membrane Strain and Tension

Guillaume T. Charras ^*, Beatrice A. Williams , Stephen M. Sims  and Mike A. Horton ^*

^* Bone and Mineral Centre, Department of Medicine, University College London, London, United Kingdom; and Canadian Institutes of Health Research Group in Skeletal Development and Remodeling, Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada

Correspondence: Address reprint requests to Dr. Guillaume Charras, Harvard Medical School, SGM 604, 250 Longwood Ave., Boston, MA 02130. Tel.: 617-432-3724; Fax: 617-432-3702; E-mail: gcharras{at}hms.harvard.edu.

Bone adapts to its environment by a process in which osteoblasts and osteocytes sense applied mechanical strain. One possible pathway for the detection of strain involves mechanosensitive channels and we sought to determine their sensitivity to membrane strain and tension. We used a combination of experimental and computational modeling techniques to gain new insights into cell mechanics and the regulation of mechanosensitive channels. Using patch-clamp electrophysiology combined with video microscopy, we recorded simultaneously the evolution of membrane extensions into the micropipette, applied pressure, and membrane currents. Nonselective mechanosensitive cation channels with a conductance of 15 pS were observed. Bleb aspiration into the micropipette was simulated using finite element models incorporating the cytoplasm, the actin cortex, the plasma membrane, cellular stiffening in response to strain, and adhesion between the membrane and the micropipette. Using this model, we examine the relative importance of the different cellular components in resisting suction into the pipette and estimate the membrane strains and tensions needed to open mechanosensitive channels. Radial membrane strains of 800% and tensions of 5 10^–4 N.m^–1 were needed to open 50% of mechanosensitive channels. We discuss the relevance of these results in the understanding of cellular reactions to mechanical strain and bone physiology.

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