title: Influence of Global and Local Membrane Curvature on Mechanosensitive Ion Channels: A Finite Element Approach.
abstract: Mechanosensitive (MS) channels are ubiquitous molecular force sensors that respond to a number of different mechanical stimuli including tensile, compressive and shear stress. MS channels are also proposed to be molecular curvature sensors gating in response to bending in their local environment. One of the main mechanisms to functionally study these channels is the patch clamp technique. However, the patch of membrane surveyed using this methodology is far from physiological. Here we use continuum mechanics to probe the question of how curvature, in a standard patch clamp experiment, at different length scales (global and local) affects a model MS channel. Firstly, to increase the accuracy of the Laplace's equation in tension estimation in a patch membrane and to be able to more precisely describe the transient phenomena happening during patch clamping, we propose a modified Laplace's equation. Most importantly, we unambiguously show that the global curvature of a patch, which is visible under the microscope during patch clamp experiments, is of negligible energetic consequence for activation of an MS channel in a model membrane. However, the local curvature (RL < 50) and the direction of bending are able to cause considerable changes in the stress distribution through the thickness of the membrane. Not only does local bending, in the order of physiologically relevant curvatures, cause a substantial change in the pressure profile but it also significantly modifies the stress distribution in response to force application. Understanding these stress variations in regions of high local bending is essential for a complete understanding of the effects of curvature on MS channels.
authors: Institute for Nanoscience and Nanotechnology, Sharif University of Technology, 89694-14588 Tehran, Iran. Omidbavi@mehr.sharif.edu.|Molecular Cardiology and Biophysics Division/Mechanosensory Biophysics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia. Omidbavi@mehr.sharif.edu.
authors: Omid
authors: O
authors: Bavi
authors: Molecular Cardiology and Biophysics Division/Mechanosensory Biophysics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia. O.Bavi@victorchang.edu.au.
authors: Charles D
authors: CD
authors: Cox
authors: Institute for Nanoscience and Nanotechnology, Sharif University of Technology, 89694-14588 Tehran, Iran. vosoughi@sharif.edu.|Biochemical &amp; Bioenvironmental Research Center (BBRC), 89694-14588 Tehran, Iran. vosoughi@sharif.edu.
authors: Manouchehr
authors: M
authors: Vossoughi
authors: Institute for Nanoscience and Nanotechnology, Sharif University of Technology, 89694-14588 Tehran, Iran. naghdabd@sharif.edu.|Department of Mechanical Engineering, Sharif University of Technology, 89694-14588 Tehran, Iran. naghdabd@sharif.edu.
authors: Reza
authors: R
authors: Naghdabadi
authors: Department of Mathematics and Bioscience, Tarbiat Modares University, Jalal Ale Ahmad Highway, 14115-111 Tehran, Iran. Y.jamali@Modares.ac.ir.|Computational physical Sciences Research Laboratory, School of Nano-Science, Institute for Research in Fundamental Sciences (IPM), 19395-5531 Tehran, Iran. Y.jamali@Modares.ac.ir.
authors: Yousef
authors: Y
authors: Jamali
authors: Molecular Cardiology and Biophysics Division/Mechanosensory Biophysics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia. b.martinac@victorchang.edu.au.|St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, NSW 2010, Australia. b.martinac@victorchang.edu.au.
authors: Boris
authors: B
authors: Martinac
keywords: continuum mechanics; finite element; local bending; mechanosensitive ion channel; membrane local curvature