2 research outputs found
Nanoparticles of Push–Pull Triphenylamine-Based Molecules for Light-Controlled Stimulation of Neuronal Activity
Organic
semiconductor materials with a unique set of properties
are very attractive for interfacing biological objects and can be
used for noninvasive therapy or detection of biological signals. Here,
we describe the synthesis and investigation of a novel series of organic
push–pull conjugated molecules with the star-shaped architecture,
consisting of triphenylamine as a branching electron donor core linked
through the thiophene π-spacer to electron-withdrawing alkyl-dicyanovinyl
groups. The molecules could form stable aqueous dispersions of nanoparticles
(NPs) without the addition of any surfactants or amphiphilic polymer
matrixes with the average size distribution varying from 40 to 120
nm and absorption spectra very similar to those of human eye retina
pigments such as rods and green cones. Variation of the terminal alkyl
chain length of the molecules forming NPs from 1 to 12 carbon atoms
was found to be an efficient tool to modulate their lipophilic and
biological properties. Possibilities of using the NPs as light nanoactuators
in biological systems or as artificial pigments for therapy of degenerative
retinal diseases were studied both on the model planar bilayer lipid
membranes and on the rat cortical neurons. In the planar bilayer system,
the photodynamic activity of these NPs led to photoinactivation of
ion channels formed by pentadecapeptide gramicidin A. Treatment of
rat cortical neurons with the NPs caused depolarization of cell membranes
upon light irradiation, which could also be due to the photodynamic
activity of the NPs. The results of the work gave more insight into
the mechanisms of light-controlled stimulation of neuronal activity
and for the first time showed that fine-tuning of the lipophilic affinity
of NPs based on organic conjugated molecules is of high importance
for creating a bioelectronic interface for biomedical applications
Multiple Mutations in the Non-Ordered Red Ω-Loop Enhance the Membrane-Permeabilizing and Peroxidase-like Activity of Cytochrome <i>c</i>
A key event in the cytochrome c-dependent apoptotic pathway is the permeabilization of the outer mitochondrial membrane, resulting in the release of various apoptogenic factors, including cytochrome c, into the cytosol. It is believed that the permeabilization of the outer mitochondrial membrane can be induced by the peroxidase activity of cytochrome c in a complex with cardiolipin. Using a number of mutant variants of cytochrome c, we showed that both substitutions of Lys residues from the universal binding site for oppositely charged Glu residues and mutations leading to a decrease in the conformational mobility of the red Ω-loop in almost all cases did not affect the ability of cytochrome c to bind to cardiolipin. At the same time, the peroxidase activity of all mutant variants in a complex with cardiolipin was three to five times higher than that of the wild type. A pronounced increase in the ability to permeabilize the lipid membrane in the presence of hydrogen peroxide, as measured by calcein leakage from liposomes, was observed only in the case of four substitutions in the red Ω-loop (M4 mutant). According to resonance and surface-enhanced Raman spectroscopy, the mutations caused significant changes in the heme of oxidized cytochrome c molecules resulting in an increased probability of the plane heme conformation and the enhancement of the rigidity of the protein surrounding the heme. The binding of wild-type and mutant forms of oxidized cytochrome c to cardiolipin-containing liposomes caused the disordering of the acyl lipid chains that was more pronounced for the M4 mutant. Our findings indicate that the Ω-loop is important for the pore formation in cardiolipin-containing membranes