β-Sheet Structured β-Amyloid(1-40) Perturbs Phosphatidylcholine Model Membranes

Planque, Maurits R.R. de; Raussens, Vincent; Contera, Sonia; Rijkers, Dirk T. S.; Liskamp, Rob M. J.; Ruysschaert, Jean Marie; Ryan, John F.; Separovic, Frances; Watts, Anthony

doi:10.1016/j.jmb.2007.02.063

Cited by 73 publications

(75 citation statements)

References 86 publications

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“…Interestingly, these current transitions frequently occur with a relatively well-defined amplitude, as highlighted in Figure 4 by applying a 50 Hz low-pass filter. Interestingly, similar "ion channel-like" modulation of the bilayer current has also been observed for cytotoxic β-amyloid oligomers, 30,31 which may suggest that silica nanospheres and nanoscale amyloid aggregates interact with lipid bilayers through a related mechanism.…”

Section: Resultsmentioning

confidence: 55%

Electrophysiological Characterization of Membrane Disruption by Nanoparticles

et al. 2011

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Direct contact of nanoparticles with the plasma membrane is essential for biomedical applications such as intracellular drug delivery and imaging, but the effect of nanoparticle association on membrane structure and function is largely unknown. Here we employ a sensitive electrophysiological method to assess the stability of protein-free membranes in the presence of silica nanospheres of different size and surface chemistry. It is shown that all the silica nanospheres permeabilize the lipid bilayers already at femtomolar concentrations, below reported cytotoxic values. Surprisingly, it is observed that a proportion of the nanospheres is able to translocate over the pure-lipid bilayer. Confocal fluorescence imaging of fluorescent nanosphere analogues also enables estimation of the particle density at the membrane surface; a significant increase in bilayer permeability is already apparent when less than 1% of the bilayer area is occupied by silica nanospheres. It can be envisaged that higher concentrations of nanoparticles lead to an increased surface coverage and a concomitant decrease in bilayer stability, which may contribute to the plasma membrane damage, inferred from lactate dehydrogenase release, that is regularly observed in nanotoxicity studies with cell cultures. This biophysical approach gives quantitative insight into nanosphere–bilayer interactions and suggests that nanoparticle–lipid interactions alone can compromise the barrier function of the plasma membrane.

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Section: Resultsmentioning

confidence: 55%

Electrophysiological Characterization of Membrane Disruption by Nanoparticles

et al. 2011

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Section: Introductionmentioning

confidence: 99%

“…However, the molecular mechanisms of the neurotoxic action of Aβ remain unknown. A growing number of observations indicate that Aβ may alter the physicochemical properties of neuronal membranes, including membrane fluidity (Muller et al, 1995) and permeability to ions and nonelectrolytes (Arispe et al, 1993;de Planque et al, 2007; Lau et al, 2006).These findings strongly suggest that at least some of the pathophysiological effects of Aβ may be mediated by Aβ-membrane interactions. Indeed, a number of studies have shown that Aβ is able to perturb lipid bilayers (Arispe et al, 1993).…”

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confidence: 99%

The interaction of amyloid Aβ(1–40) with lipid bilayers and ganglioside as studied by 31P solid-state NMR

Nakazawa

Suzuki

Williamson

et al. 2009

Chemistry and Physics of Lipids

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Amyloid β-peptide (Aβ) is a major component of plaques in Alzheimer's disease, and formation of senile plaques has been suggested to originate from regions of neuronal membrane rich in gangliosides. We analyzed the mode of interaction of Aβ with lipid bilayers by multinuclear NMR using 31 P nuclei. We found that Aβ (1-40) strongly perturbed the bilayer structure of dimyristoylphosphatidylcholine (DMPC), to form a non-lamellar phase (most likely micellar). The ganglioside GM1 potentiated the effect of Aβ (1-40), as viewed from 31 P NMR. The difference of the isotropic peak intensity between DMPC/Aβ and DMPC/GM1/Aβ suggests a specific interaction between Aβ and GM1. We show that in the DMPC/GM1/Aβ system there are three lipid phases, namely a lamellar phase, a hexagonal phase and non-oriented lipids. The latter two phases are induced by the presence of the Aβ peptide, and facilitated by GM1.Key Words: β-amyloid, Alzheimer's disease, NMR, GM1-ganglioside, lipid bilayer Abbreviations: DMPC: dimyristoylphosphatidylcholine, Aβ: Amyloid β-peptide, AD:Alzheimer's disease, NMR: Nuclear Magnetic Resonance 3 IntroductionAlzheimer's disease (AD) is a devastating neurodegenerative disease affecting up to 15 million individuals worldwide. The brains of Alzheimer's disease patients are characterized by fibrillar amyloid plaques that are associated with progressive deposits (Iversen et al., 1995). The principal component of amyloid deposits is a 39-42 amino acid residue peptide, Aβ (Glenner et al., 1984;Masters et al., 1985), a product of proteolytic processing of a much larger amyloid precursor protein encoded by a gene on chromosome 21 (Kang et al., 1987). Several spectroscopic investigations have clarified the structure of the fibrils, which form a 'cross-β sheet' structure (Kirschner et al., 1986;Petkova et al., 2002;Petkova et al., 2006). Moreover, a link between Aβ and AD neuropathological lesions is demonstrated by the toxicity of aggregated Aβ to neuronal cells in culture (Lambert et al., 1998) and in aged brain (Geula et al., 1998). However, the molecular mechanisms of the neurotoxic action of Aβ remain unknown. A growing number of observations indicate that Aβ may alter the physicochemical properties of neuronal membranes, including membrane fluidity (Muller et al., 1995) and permeability to ions and nonelectrolytes (Arispe et al., 1993;de Planque et al., 2007; Lau et al., 2006).These findings strongly suggest that at least some of the pathophysiological effects of Aβ may be mediated by Aβ-membrane interactions. Indeed, a number of studies have shown that Aβ is able to perturb lipid bilayers (Arispe et al., 1993). Interest in studies of the interaction between Aβ and constituents of brain membranes has been further stimulated by the identification of an Aβ-GM1 ganglioside-bound form in AD brain (Chi et al., 2007; Kakio et al., 2002;Yanagisawa et al., 1995). 4Gangliosides (Brocca et al., 1997; Kasahara et al., 2001) are sialic acid-containing glycosphingolipids and consist of two main components: a hydrophobic...

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“…In fact, there is ample evidence for purified proteins to induce non-specific ion currents in artificial membranes. For example, proteins as diverse as amyloid peptides, tau and transferrin can all induce transmembrane currents in artificial bilayers, without any evidence of physiological relevance (Aguilera et al, 2003;de Planque et al, 2007;Kagan et al, 2004;Patel et al, 2015). Thus, the CLIC 'Cl − channel hypothesis' appears highly questionable, especially as convincing in vivo validation is still absent after more than two decades, and implies that the 'Cl − intracellular channel' terminology might need to be revised.…”

Section: Enzymatic Activity Of Clicsmentioning

confidence: 99%

Emerging biological roles of Cl− intracellular channel proteins

Argenzio

Moolenaar

2016

Journal of Cell Science

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Cl− intracellular channels (CLICs) are a family of six evolutionary conserved cytosolic proteins that exist in both soluble and membraneassociated forms; however, their functions have long been elusive. Soluble CLICs adopt a glutathione S-transferase (GST)-fold, can induce ion currents in artificial membranes and show oxidoreductase activity in vitro, but there is no convincing evidence of CLICs having such activities in vivo. Recent studies have revealed a role for CLIC proteins in Rho-regulated cortical actin dynamics as well as vesicular trafficking and integrin recycling, the latter of which are under the control of Rab GTPases. In this Commentary, we discuss the emerging roles of CLIC proteins in these processes and the lessons learned from genetargeting studies. We also highlight outstanding questions regarding the molecular function(s) of these important but still poorly understood proteins.

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β-Sheet Structured β-Amyloid(1-40) Perturbs Phosphatidylcholine Model Membranes

Cited by 73 publications

References 86 publications

Electrophysiological Characterization of Membrane Disruption by Nanoparticles

Electrophysiological Characterization of Membrane Disruption by Nanoparticles

The interaction of amyloid Aβ(1–40) with lipid bilayers and ganglioside as studied by 31P solid-state NMR

Emerging biological roles of Cl− intracellular channel proteins

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