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Roseville, Australia

Valenzuela S.M.,University of Technology, Sydney | Alkhamici H.,University of Technology, Sydney | Brown L.J.,Macquarie University | Almond O.C.,University of Technology, Sydney | And 8 more authors.
PLoS ONE | Year: 2013

The Chloride Intracellular ion channel protein CLIC1 has the ability to spontaneously insert into lipid membranes from a soluble, globular state. The precise mechanism of how this occurs and what regulates this insertion is still largely unknown, although factors such as pH and redox environment are known contributors. In the current study, we demonstrate that the presence and concentration of cholesterol in the membrane regulates the spontaneous insertion of CLIC1 into the membrane as well as its ion channel activity. The study employed pressure versus area change measurements of Langmuir lipid monolayer films; and impedance spectroscopy measurements using tethered bilayer membranes to monitor membrane conductance during and following the addition of CLIC1 protein. The observed cholesterol dependent behaviour of CLIC1 is highly reminiscent of the cholesterol-dependent-cytolysin family of bacterial pore-forming proteins, suggesting common regulatory mechanisms for spontaneous protein insertion into the membrane bilayer. © 2013 Valenzuela et al. Source

Monfared S.M.,University of British Columbia | Krishnamurthy V.,University of British Columbia | Cornell B.C.,Surgical Diagnostics Pty Ltd.
Proceedings of the IEEE Conference on Decision and Control | Year: 2010

This paper deals with the construction and analysis of distributed dynamical models for a novel biosensor that exploits the molecular switching mechanism of biological ion channels. The rate of change of the concentration of the chemical species in the biosensor are given by a system of nonlinear ordinary differential equations in the reaction-rate limited region of operation. When the transport rate of analyte to the biosensor surface is comparable to the intrinsic reaction rates, the dynamics of the biosensor are explained accurately using a two dimensional advection diffusion parabolic partial differential equation. When the rate of transport of analyte to the biosensor surface is much slower than the intrinsic reaction rates the biosensor is said to be operating under mass transport limited conditions. Under these conditions a system of coupled ordinary differential equations and the mass transport coefficient model the dynamics of the biosensor accurately. The equivalent mathematical models are shown to produce accurate data under the required operating conditions by comparison with experimental data. ©2010 IEEE. Source

Martinac B.,Victor Chang Cardiac Research Institute | Martinac B.,University of New South Wales | Nomura T.,Victor Chang Cardiac Research Institute | Chi G.,University of Queensland | And 14 more authors.
Antioxidants and Redox Signaling | Year: 2014

Significance: Sensations of touch and hearing are manifestations of mechanical contact and air pressure acting on touch receptors and hair cells of the inner ear, respectively. In bacteria, osmotic pressure exerts a significant mechanical force on their cellular membrane. Bacteria have evolved mechanosensitive (MS) channels to cope with excessive turgor pressure resulting from a hypo-osmotic shock. MS channel opening allows the expulsion of osmolytes and water, thereby restoring normal cellular turgor and preventing cell lysis. Recent Advances: As biological force-sensing systems, MS channels have been identified as the best examples of membrane proteins coupling molecular dynamics to cellular mechanics. The bacterial MS channel of large conductance (MscL) and MS channel of small conductance (MscS) have been subjected to extensive biophysical, biochemical, genetic, and structural analyses. These studies have established MscL and MscS as model systems for mechanosensory transduction. Critical Issues: In recent years, MS ion channels in mammalian cells have moved into focus of mechanotransduction research, accompanied by an increased awareness of the role they may play in the pathophysiology of diseases, including cardiac hypertrophy, muscular dystrophy, or Xerocytosis. Future Directions: A recent exciting development includes the molecular identification of Piezo proteins, which function as nonselective cation channels in mechanosensory transduction associated with senses of touch and pain. Since research on Piezo channels is very young, applying lessons learned from studies of bacterial MS channels to establishing the mechanism by which the Piezo channels are mechanically activated remains one of the future challenges toward a better understanding of the role that MS channels play in mechanobiology. Antioxid. Redox Signal. 20, 952-969. © 2014 Mary Ann Liebert, Inc. Source

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