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Research Directory
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UNIVERSITY OF
BRITISH
COLUMBIA
DEPARTMENT OF
PHYSICS AND
ASTRONOMY
6224 Agricultural Rd., Vancouver, B.C., V6T 1Z1, Canada
Phone: (604)822-3853 Fax: (604)822-5324
Benjamin A.
Smith
Honorary Postdoctoral Fellow
Biophysics
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Office: |
Purdy Pavilion G-30 |
604-822-7579 |
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Lab: |
604-822-7579 |
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Research:
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Area: Experimental Biophysics
Field: Membrane & Cellular Mechanics
Topics: lipid bilayers, dynamic rupture , non-linear elasticity, lipid-cholesterol interactions, antimicrobial peptides
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| | | Current location:
Gelles Lab
Brandeis University, Biochemistry Department
bsmith -at- brandeis -dot- edu
http://www.bio.brandeis.edu/~gelles/
The strength and stability of lipid membranes are of fundamental importance to the survival and functions of biological cells. The focus of my postdoctoral research with Dr. Evan Evans at the University of British Columbia is the use of micropipette aspiration techniques to investigate the dynamic mechanical properties (elasticity, rupture strength, lifetime, viscosity, etc.) of phospholipid bilayers containing cholesterol, a major component of cellular plasma membranes. Statistical and thermo-mechanical models are developed in parallel with novel experimental methods to identify the primary molecular determinants of membrane strength. For example, we use an anharmonic relationship between bilayer surface pressure and area expansion, based on polymer statistical mechanics, to model the nonlinear elasticity of lipid membranes. This relation is then used as an elastic transducer for measuring the energetics of lipid-cholesterol interactions. The increased elastic strength imparted by cholesterol is described using the equilibrium thermodynamics of lipid-cholesterol condensed cluster formation. The success of this study ascertains that cholesterol effectively squeezes the heat (conformational entropy) out of lipid hydrocarbon chains, with a measurable dependence on tension, temperature, and the number of unsaturated bonds per chain. These measurements are crucial to the understanding of membrane organization and could be extended to quantify lipid-protein interactions.
Antimicrobial peptides provide an innate immune defense against pathogen infestation to vertebrates, plants, and insects. Using dynamic rupture tension spectroscopy and nonlinear elasticity analysis, we are currently investigating the ability of these peptides is to disrupt, weaken, and permeablize model bacterial and eukaryotic membranes. We expect that different classes of membrane-active peptides act by different mechanisms (e.g. insertion, pore formation, or detergent-like destabilization), which could be described quantitatively by the above techniques. Impoving our understanding of the mechanisms of action and toxicity of antimicrobial peptides is vital to the development of novel therapeutics to treat antibiotic-resistant infection.
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Selected Publications:
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Smith BA, Rawicz W, Evans E. Mechanical strengths and lifetimes of PC vesicles in dilute solutions of the antimicrobial peptide melittin. (2008) Biophys. J. ... in preparation.
Smith BA, McIntosh TJ, Evans E. Using hyper-stretch of vesicle bilayers to characterize the energetics of lipid-cholesterol interactions. (2008) Biophys. J. ... in preparation.
Smith BA, Evans E. Using hyper-stretch of vesicle bilayers to characterize the non-linear dependence of lipid surface pressure on area per molecule. (2008) Biophys. J. ... in preparation.
Rawicz W*, Smith BA*, McIntosh TJ, Simon SA, Evans E. Elasticity, strength, and water permeability of bilayers that contain raft microdomain-forming lipids. (2008) Biophys. J. 94(12):4725-4736. (* First and second authors contributed equally)
Smith BA, Roy H, DeKoninck P, Grütter P, DeKoninck Y. Dendritic spine viscoelasticity and soft-glassy nature: balancing dynamic remodeling with structural stability. (2007) Biophys. J. 92(4):1419-1430.
Smith BA, Tolloczko B, Martin JG, Grütter P. Probing the viscoelastic behavior of cultured airway smooth muscle cells with atomic force microscopy: stiffening induced by contractile agonist. (2005) Biophys. J. 88(4):2994-3007.
Anselmetti DA, Fritz J, Smith BA, Fernandez-Busquets X. Single molecule DNA biophysics with atomic force microscopy. (2000) Single Molecules. 1(1):53-58. |
Last updated 2009-05-28 09:27:52
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