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Paradoxical Lipid Dependence of Pores Formed by the Escherichia coli -Hemolysin in Planar Phospholipid Bilayer Membranes

Laura Bakás  , Alexandr Chanturiya ^*, Vanesa Herlax  and Joshua Zimmerberg ^*

^* Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, 1900 La Plata, Argentina; and Instituto de Investigaciones Bioquímicas, La Plata, INIBIOLP, Argentina

Correspondence: Address reprint requests to Joshua Zimmerberg, Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Tel.: 301-496-6571; Fax: 301-402-0263; E-mail: joshz{at}helix.nih.gov.

-Hemolysin (HlyA) is an extracellular protein toxin (117 kDa) secreted by Escherichia coli that targets the plasma membranes of eukaryotic cells. We studied the interaction of this toxin with membranes using planar phospholipid bilayers. For all lipid mixtures tested, addition of nanomolar concentrations of toxin resulted in an increase of membrane conductance and a decrease in membrane stability. HlyA decreased membrane lifetime up to three orders of magnitude in a voltage-dependent manner. Using a theory for lipidic pore formation, we analyzed these data to quantify how HlyA diminished the line tension of the membrane (i.e., the energy required to form the edge of a new pore). However, in contrast to the expectation that adding the positive curvature agent lysophosphatidylcholine would synergistically lower line tension, its addition significantly stabilized HlyA-treated membranes. HlyA also appeared to thicken bilayers to which it was added. We discuss these results in terms of models for proteolipidic pores.