Molecular Interactions of Alzheimer's Aβ Protofilaments with Lipid Membranes

Tofoleanu, Florentina; Buchete, Nicolae‐Viorel

doi:10.1016/j.jmb.2011.12.063

Cited by 66 publications

(102 citation statements)

References 101 publications

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“…On a longer time scale, the Aβ monomer may adopt a largely helical structure inside the membrane. 28 Pannuzzo et al performed multiscale coarsegrained and atomistic MD simulations to study the interaction of Aβ(1−40) with the POPC bilayer in the microsecond domain. They found that as Aβ peptides adsorbed and aggregated at the POPC bilayer, an obvious membrane curvature was induced with the Aβ helical structure maintained in the aggregated form.…”

Section: ■ Discussionmentioning

confidence: 99%

“…22 −24 Membrane has been shown to possess physical properties that facilitate the adsorption of peptides/ proteins without significantly affecting their translational mobility 9,25,26 as well as the electrostatic interaction between the lipids and Aβ. 27,28 As a result, additional molecules can be accumulated through interpeptide interaction along the membrane surface, eventually forming nuclei that are critical for fibril formation. Various lipid membranes have been shown to enrich Aβ peptides, facilitating misfolding of Aβ into toxic oligomers at rates considerably faster than in a membrane-free environment.…”

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confidence: 99%

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Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Zhang

Gong

et al. 2015

Biochemistry

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The amyloid cascade hypothesis links the amyloid-β (Aβ) peptide aggregation to neuronal cell damage and ultimately the etiology of Alzheimer's disease (AD). Although Aβ aggregation has been known to accelerate at cell membranes, the exact mechanism of Aβ peptide deposition and the involvement of extracellular species are still largely unclear. Using surface plasmon resonance (SPR) and atomic force microscopy (AFM), we demonstrate that Ca(2+) ions, in conjunction with lipid bilayer, lower the threshold concentration for Aβ aggregation (>a few micromolar in vitro) to physiological levels (low nanomolar). Circular dichroism spectroscopy reveals that Ca(2+) ions and the lipid bilayer concertedly accelerate the conformational change or misfolding of Aβ peptides. Molecular dynamics calculation indicates that Ca(2+) is sandwiched between Glu-22 of Aβ and the lipid phosphate group. SPR experiments conducted using an E22G mutant confirmed the strong interaction among Ca(2+), Aβ(1-42), and the phospholipid bilayer. With the C- and N-termini of the Aβ dimer fully exposed for the attachment of additional Aβ molecules, fibrils formed with the Ca(2+)-anchored Aβ nuclei appear to interact with lipid bilayers differently from those preformed in solution. Thus, similar to the role of Ca(2+) in enriching islet amyloid polypeptides in the pancreas of diabetic patients ( Biophys. J. 2013 , 104 , 173 - 184 ) and the "Ca(2+) bridge" in mediating membrane interaction with α-synuclein in the Parkinson's disease ( Biochemistry , 2006 , 45 , 10947 - 10956 ), the influence of Ca(2+) on the Aβ adsorption at cell membranes, which leads to neuronal membrane damage in AD, cannot be overlooked.

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Section: ■ Discussionmentioning

confidence: 99%

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confidence: 99%

Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Zhang

Gong

et al. 2015

Biochemistry

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“…Total atom numbers for each system including water molecules are reported in Table 1. Systems were prepared for MD simulation as described in our previous papers using also similar NPT MD studies [38–40] of larger amyloid peptides such as Alzheimer’s amyloid-beta (Aβ, [41–43]) or human amylin (hIAPP, [44]).…”

Section: Methodsmentioning

confidence: 99%

Conformational dynamics and aggregation behavior of piezoelectric diphenylalanine peptides in an external electric field

Kelly

Northey

Ryan

et al. 2015

Biophysical Chemistry

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Aromatic peptides such as diphenylalanine (FF) have the characteristic capacity to self-assemble into ordered nanostructures such as peptide nanotubes, which are biocompatible, thermally and chemically stable, and have strong piezoelectric activity and high mechanical strength. The physical properties of FF aggregates open up a variety of potential biomedical applications. Electric fields are commonly applied to align FF nanotubes, yet little is known about the effect of the electric field on the assembly process. Using all-atom molecular dynamics with explicit water molecules, we probe the conformational dynamics of individual, solvated FF molecules with both charged and neutral ends, to account for different possible pH conditions. With charged ends, the FF molecules show more complex dynamics, experiencing three main conformational states (cis, trans and extended). We first examine the structural response of FF monomers to the application of a constant external electric field over a range of intensities. We also probe the aggregation mechanism of FF peptides, both with and without an externally applied electric field, and find that the presence of even relatively weak fields can accelerate the formation of ordered FF aggregates, primarily by facilitating the alignment of individual molecular dipole moments. The correlation between the strength of the external electric field and the local dipolar interactions is modulated both by the conformational response of individual FF peptides (e.g. backbone stretching, hydrogen bonds and relative alignment of aromatic sidechains) and by the response of neighboring FF and water molecules. These field-dependent observations may facilitate future studies on the controlled formation of nano-structured aggregates of piezoelectric peptides and the understanding of their specific electromechanical properties.

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“…Fibrillar and globular-like Aβ oligomers can cause both non-specific and specific ion leakage, either by membrane thinning or by forming pore-like trans-membrane structures that may conduct ions. Tofoleanu and Buchete, probed the molecular interactions between preformed fibrillar Aβ oligomers and lipid bilayers, in the presence of explicit water molecules, using all-atom MD simulations (see Figure 8) (Tofoleanu & Buchete, 2012b). These interactions play an important role in the stability and function of both Aβ fibrils, and of the contiguous cellular membrane (Tofoleanu & Buchete, 2012a; Tofoleanu & Buchete, 2012b).…”

Section: Amyloids and Membranesmentioning

confidence: 99%

Membrane Protein Structure, Function, and Dynamics: a Perspective from Experiments and Theory

et al. 2015

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Membrane proteins mediate processes that are fundamental for the flourishing of biological cells. Membrane-embedded transporters move ions and larger solutes across membranes, receptors mediate communication between the cell and its environment and membrane-embedded enzymes catalyze chemical reactions. Understanding these mechanisms of action requires knowledge of how the proteins couple to their fluid, hydrated lipid membrane environment. We present here current studies in computational and experimental membrane protein biophysics, and show how they address outstanding challenges in understanding the complex environmental effects on the structure, function and dynamics of membrane proteins.

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Molecular Interactions of Alzheimer's Aβ Protofilaments with Lipid Membranes

Cited by 66 publications

References 101 publications

Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Conformational dynamics and aggregation behavior of piezoelectric diphenylalanine peptides in an external electric field

Membrane Protein Structure, Function, and Dynamics: a Perspective from Experiments and Theory

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Molecular Interactions of Alzheimer's Aβ Protofilaments with Lipid Membranes

Cited by 66 publications

References 101 publications

Ca2+ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Ca2+ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Conformational dynamics and aggregation behavior of piezoelectric diphenylalanine peptides in an external electric field

Membrane Protein Structure, Function, and Dynamics: a Perspective from Experiments and Theory

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Product

Resources

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Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration