Synthetic Hydraphile Channels of Appropriate Length Kill Escherichia coli

Leevy, W. Matthew; Donato, Gina M.; Ferdani, Riccardo; Goldman, William E.; Schlesinger, Paul H.; Gokel, George W.

doi:10.1021/ja017052o

Cited by 91 publications

(96 citation statements)

References 21 publications

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“…The results from the simulations provided details about the hydraphile-membrane interactions and confirmed that hydraphiles with the appropriate length of the alkyl chain linkers between the crown-ether moieties adopt a membrane-spanning conformation. The resulting picture is consistent with a membrane-spanning model proposed by Leevy et al [242].…”

Section: Protein Insertion Into Membranessupporting

confidence: 91%

Mesoscopic models of biological membranes

Venturoli¹,

et al. 2006

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Phospholipids are the main components of biological membranes and dissolved in water these molecules self-assemble into closed structures, of which bilayers are the most relevant from a biological point of view. Lipid bilayers are often used, both in experimental and by theoretical investigations, as model systems to understand the fundamental properties of biomembranes. The properties of lipid bilayers can be studied at different time and length scales. For some properties it is sufficient to envision a membrane as an elastic sheet, while for others it is important to take into account the details of the individual atoms. In this review, we focus on an intermediate level, where groups of atoms are lumped into pseudo-particles to arrive at a coarse-grained, or mesoscopic, description of a bilayer, which is subsequently studied using molecular simulation.The aim of this review is to compare various strategies to coarse grain a biological membrane. The conclusion of this comparison is that there can be many valid different strategies, but that the results obtained by the various mesoscopic models are surprisingly consistent. A second objective of this review is to illustrate how mesoscopic models can be used to obtain a better understanding of experimental systems. The advantage of coarse-grained models is that these can be simulated very efficiently, so that phenomena involving large systems, or requiring a large number of simulations, can be studied in detail. This is illustrated with the study of the relation between the phase behavior of a membrane and the structure of the phospholipids, and the membrane structural changes due to molecules (such as alcohols, cholesterol and anesthetics) adsorbed to the membrane. We then discuss the effect of transmembrane peptides on the local structure of a membrane and the mechanism of vesicle fusion and fission.

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Section: Protein Insertion Into Membranessupporting

confidence: 91%

Mesoscopic models of biological membranes

Venturoli¹,

et al. 2006

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“…[6][7][8][9]12 These channels show open-shut behavior characteristic of protein channels. They exhibit selectivity for cations over anions and for Na + over K + .…”

Section: Use Of Hydraphiles As a Membrane Probementioning

confidence: 99%

Dynamic Assessment of Bilayer Thickness by Varying Phospholipid and Hydraphile Synthetic Channel Chain Lengths

2004

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A library of "hydraphile" synthetic ion channel analogues that differ in overall length from ∼28-58 Å has been prepared. A new and convenient ion-selective electrode (ISE) method was used to assay Na + release. Liposomes were formed from three different phospholipids: 1,2-dimyristoleoyl-snglycero-3-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-dierucoyl-sn-glycero-3-phosphocholine (DEPC). The acyl chains of the lipids comprise cisunsaturated 14:1, 18:1, or 22:1 residues, respectively. Sodium release was measured for each liposome system with each of the synthetic channels. Peak activity was observed for shorter channels in liposomes formed from DMPC and for longer channels in DEPC. A separate study was then conducted in DMPC liposomes in the presence of the putative membrane-thickening agents cholesterol and decane. Peak activity was clearly shifted to longer channel lengths upon addition of 20 or 40 mol % cholesterol or n-decane to the liposome preparation.

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“…E. coli are small (~0.5×2 µm), but they are readily detectable by optical microscopy. The suspension above was examined with a fluorescent microscope and fluorescence was clearly identified in the periphery of the organism and not within it to any significant extent [20]. This is illustrated in Figure 5.…”

Section: Resultsmentioning

confidence: 98%

“…Ion concentrations are closely regulated in all vital cells, even in the simplest microbes. We reasoned, and later demonstrated [19], that hydraphiles can insert in microbial membranes [20]. If so, they should disrupt the natural ion balance (ion homeostasis) of these organisms, potentially with toxic effect.…”

Section: Resultsmentioning

confidence: 99%