Seventh International Congress of Comparative Physiology and Biochemistry Salvador, Bahia, Brazil, August 12–16, 2007 3. Comparative aspects in mechanobiology: From bacteria to human 3.1. Variety and integration of mechanotransduction in cells Sokabe , M. Nagoya University Graduate School of Medicine, Japan msokabe@med.nagoya-.ac.jp Mechanotransduction is ubiquitous in our body. It is functioning not only in specialized mechanoreceptors like inner ear hair cells and visceral baroreceptors but also in ordinary cells by which cells can regulate properly their volume, shape and motility. In the past decade, we have partially understood biophysical mechanisms of mechanotransduction based on the molecular identification of mechanosensitive (MS) ion channels that are the only established class of mechanosensors to date. Among them, bacterial MS channels are the best studied ones with known 3D structure and activated simply by the increased membrane tension accompanied with cell inflation upon hypotonic shock. On the other hand, eukaryotic cells have evolved more complicated mechanotransduction systems. We found that some eukaryotic MS channels are associated with cytoskeleton/focal contact complex, by which they obtain increased mechanosensitivity and force–direction sensitivity. Furthermore, we recently discovered that stress fiber, an actomyosin-based cytoskeleton, can act as a mechanosensor in concert with focal contact. It seems likely that spatiotempo- rally regulated integration of such a variety of mechanosensors, MS channels, cytoskeletons and focal proteins actualizes the complicated cell responses such as morphogenesis and migra- tion. A cell–molecular model of this idea will be presented. doi:10.1016/j.cbpa.2007.06.030 3.2. Lipid–protein interactions and the gating of prokaryotic mechanosensitive channels Perozo , E., Cortes, D.M., Vasquez, V., Wu, J., Pornthep, S., and Martinac, B. Department of Biochemistry and Molecular Biology, Institute for Molecular Pediatric Science, University of Chicago, Chicago, IL 60637, USA eperozo@uchicago.edu Mechanosensitive channels act as membrane-embedded mechano-electrical switches, opening a large water-filled pore in response to lipid bilayer deformations. This process is critical in the response of prokaryotic organisms to changes in the osmolarity of their surroundings. To probe the molecular mechanism of how mechanical force gates MscL, we have recently evaluated two physical mechanisms as triggers of MscL gating by bilayer deformation forces: (i) the energetic cost of protein–bilayer hydrophobic mismatches and (ii) the geometric consequences of bilayer intrinsic curvature. Struc- tural changes in MscL from Escherichia coli were studied under zero external transbilayer pressures using both the patch clamp and EPR spectroscopic approaches. To examine the role of hydrophobic mismatch in MscL gating, we recorded the activity of MscL in phosphatidylcholine bilayers of different thickness ranging from 10 (PC10) to 20 (PC20) hydrocarbons per acyl chain. We found that decreasing bilayer thickness lowered MscL activation energy and stabilized a structurally distinct closed channel intermediate. Although hydrophobic mismatch alone was unable to open the channel, the importance of hydrophobic mismatch for MscL mechanosensitivity results from stretch induced bilayer thinning, which stabilizes the open conformation of MscL due to a better hydrophobic match with the open compared to the closed conformation of the channel. Changes in membrane intrinsic curvature induced by the Comparative Biochemistry and Physiology, Part A 148 (2007) S13 – S16 www.elsevier.com/locate/cbpa doi:10.1016/j.cbpa.2007.06.029