Amyloid
β, Aβ(1–42), is a component of senile
plaques present in the brain of Alzheimer’s disease patients
and one of the main suspects responsible for pathological consequences
of the disease. Herein, we directly visualize the Aβ activity
toward a brain-like model membrane and demonstrate that this activity
strongly depends on the Aβ oligomer size. PeakForce quantitative
nanomechanical mapping mode of atomic force microscopy imaging revealed
that the interaction of large-size (LS) Aβ oligomers, corresponding
to high-molecular-weight Aβ oligomers, with the brain total
lipid extract (BTLE) membrane resulted in accelerated Aβ fibrillogenesis
on the membrane surface. Importantly, the fibrillogenesis did not
affect integrity of the membrane. In contrast, small-size (SS) Aβ
oligomers, corresponding to low-molecular-weight Aβ oligomers,
created pores and then disintegrated the BTLE membrane. Both forms
of the Aβ oligomers changed nanomechanical properties of the
membrane by decreasing its Young’s modulus by ∼45%.
Our results demonstrated that both forms of Aβ oligomers induce
the neurotoxic effect on the brain cells but their action toward the
membrane differs significantly.
A new
redox conducting polymer, viz. poly[meso-N,N′-bis(salicylidene)-2,3-butanediaminonickel(II)],
poly[meso-Ni(II)-SaldMe], belonging to the Schiff base polymer family,
was electrochemically synthesized. The charge transfer and polymerization
mechanism were unraveled by simultaneous cyclic voltammetry (CV) and
in situ UV–vis, FTIR-ATR, and ex situ low-temperature ESR spectroscopy.
With the latter, a short-living paramagnetic transient form of electro-oxidized
poly[meso-Ni(II)-SaldMe] was detected. This form was identified as
the bisphenolic radical cation. In situ UV–vis and FTIR-ATR
spectroelectrochemistry measurements revealed that the charge transfer
of the polymer involved bisphenolic radical cation formation at the
potential lower than 0.80 V vs Ag/Ag+ and then dication
formation at the potential exceeding 0.80 V. The proposed mechanism
of electropolymerization of meso-N,N′-bis(salicylidene)-2,3-butanediaminonickel(II), meso-Ni(II)-SaldMe,
involves two steps. First, electro-oxidation of the monomer results
in bisphenolic radical cation generation, and then mutual binding
of these radicals at the para positions of aromatic
rings is activated by electron-donating phenol moieties. In this electropolymerization,
the Ni(II) metal center played the role of a template providing planarity
to the monomer molecule. Structures responsible for the charge transfer
in the polymer and formed during electropolymerization were modeled
with quantum chemistry calculations using the DFT method at the PBE
level. The resulting polymer film was highly conducting and stable
with respect to potential multicycling under cyclic voltammetry conditions,
from 0 to 1.3 V vs Ag/Ag+. Under these conditions, it changes
color from yellow through orange to russet for its neutral, bisphenolic
radical cation, and bisphenolic dication form, respectively. High
electrochemical stability and a wide potential range of electroactivity
(0.40–1.30 V vs Ag/Ag+) of the polymer are very
promising for its application as a new electrochromic electrode material
for supercapacitors. That is, an anode composed of poly[meso-Ni(II)-SaldMe]
can serve as an internal charging–discharging indicator in
these supercapacitors.
The
“gate effect” mechanism for conductive molecularly
imprinted polymer (MIP) film coated electrodes was investigated in
detail. It was demonstrated that the decrease of the DPV signal for
the Fe(CN)6
4–/Fe(CN)6
3– redox probe with the increase of the p-synephrine target analyte concentration in solution at the polythiophene
MIP-film coated electrode did not originate from swelling or shrinking
of the MIP film, as it was previously postulated, but from changes
in the electrochemical process kinetics. The MIP-film coated electrode
was examined with cyclic voltammetry (CV), differential pulse voltammetry
(DPV), electrochemical impedance spectroscopy (EIS), and surface plasmon
resonance (SPR). The MIP-film thickness in the absence and in the
presence of the p-synephrine analyte was examined
with in situ AFM imaging. Moreover, it was demonstrated that doping
of the MIP film was not affected by p-synephrine
binding in MIP-film molecular cavities. It was concluded that the
“gate effect” was most likely caused by changes in radical
cation (polaron) mobility in the film.
Alzheimer's disease (AD) is characterized by progressive neurodegeneration associated with amyloid β (Aβ) peptide aggregation. The aggregation of Aβ monomers (AβMs) leads to the formation of Aβ oligomers (AβOs), the neurotoxic Aβ form, capable of permeating the cell membrane. Here, we investigated the effect of a fluorene-based active drug candidate, named K162, on both Aβ aggregation and AβO toxicity toward the bilayer lipid membrane (BLM). Electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM), and molecular dynamics (MD) were employed to show that K162 inhibits AβOs-induced BLM permeation, thus preserving BLM integrity. In the presence of K162, only shallow defects on the BLM surface were formed. Apparently, K162 modifies Aβ aggregation by bypassing the formation of toxic AβOs, and only nontoxic AβMs, dimers (AβDs), and fibrils (AβFs) are produced. Unlike other Aβ toxicity inhibitors, K162 preserves neurologically beneficial AβMs. This unique K162 inhibition mechanism provides an alternative AD therapeutic strategy that could be explored in the future.
The behavior, secondary structure, and orientation of a recently discovered bacteriocin-like peptide BacSp222 in a lipid model system supported at a gold electrode was investigated by chronocoulometry, polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS), and attenuated total reflectance infrared (ATR-IR) spectroscopy. The IR spectra show that the secondary structure of BacSp222 is predominantly α-helical. Analysis of the spectra in the amide I region shows that the α-helical fragment of the peptide is inserted into bilayer at the potential range at which the bilayer is stable and attached to the Au(111) surface, i.e., from -0.5 to 0.3 V vs Ag/AgCl. Insertion of BacSp222 to the membrane significantly changes the conformation of the acyl chains of lipid molecules, from all-trans to partially melted; however, the chains become less tilted. Based on these results, we propose that BacSp222 interacts with the DMPC bilayer through the barrel-stave pore formation. In this model, α-helix of BacSp222 inserts into the membrane with an angle between the α-helix axis and membrane normal equal to ∼18°. The changes in orientation of the α-helical fragment of the peptide indicate that the orientation of BacSp222 with respect to the bilayer surface is potential-dependent. The peptide is inserted into the membrane driven by the electrostatic field generated by negative charge at the metal surface. It is not inserted at negative potentials where the membrane is detached from the metal and no longer exposed to the electrostatic field of the metal.
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