Highly sensitive gating in pH-responsive nanochannels as a result of ionic bridging and nanoconfinement

2018 ◽  
Author(s):  
Luis G. Lopez ◽  
Rikkert J. Nap
Keyword(s):  
Microphase Separation ◽  
Logic Gates ◽  
Ion Concentration ◽  
Molecular Organization ◽  
Bulk Solution ◽  
Dependent Manner ◽  
Stimuli Responsive ◽  
Ph Responsive ◽  
Concentration Dependent Manner ◽  
Ph Responsive Polymers

Sensitive switching between OFF and ON states is a desirable feature in stimuli-responsive nanopores and nanochannels. In this work, we show that nanogates modified with weak polyelectrolytes can be controlled by multivalent counterions and, more remarkably, can exhibit sensitive pH-gating due to an interplay between ionic bridging and nanoconfinement. We demonstrate these general features by systematically studying the effects of Ca2+ binding on the molecular organization and transport properties of poly(acrylic acid)-functionalized nanochannels. To this end, we extend and apply a molecular theory that has been successfully used in the past to describe and predict the behavior of pH-responsive polymers. Two main results emerge from the present study: First, the addition of Ca2+ to the bulk solution changes—in a concentration-dependent manner—both the ionization and structural state of the end-tethered polymers, affecting, respectively, the ionic conductivity and physical opening of the nanochannel. Second, in the presence of Ca2+ and under specific nanoconfinement conditions, the grafted channel can exhibit a sensitive response to pH in the transition between closed and open states. We attribute this sensitivity to bistability in the system. Our results also indicate that the polymer layer can undergo a microphase separation when the brush collapses on the nanochannel walls. Taken together, these findings suggest the possibility of designing nanogates that can respond to marginal changes in pH or multivalent ion concentration. Such nanodevices may be used as logic gates or for any application that requires a sensitive control over the ions, molecules, or nanoparticles flowing through them.

Highly sensitive gating in pH-responsive nanochannels as a result of ionic bridging and nanoconfinement

2018 ◽  
Author(s):  
Luis G. Lopez ◽  
Rikkert J. Nap
Keyword(s):  
Microphase Separation ◽  
Logic Gates ◽  
Ion Concentration ◽  
Molecular Organization ◽  
Bulk Solution ◽  
Dependent Manner ◽  
Stimuli Responsive ◽  
Ph Responsive ◽  
Concentration Dependent Manner ◽  
Ph Responsive Polymers

Sensitive switching between OFF and ON states is a desirable feature in stimuli-responsive nanopores and nanochannels. In this work, we show that nanogates modified with weak polyelectrolytes can be controlled by multivalent counterions and, more remarkably, can exhibit sensitive pH-gating due to an interplay between ionic bridging and nanoconfinement. We demonstrate these general features by systematically studying the effects of Ca2+ binding on the molecular organization and transport properties of poly(acrylic acid)-functionalized nanochannels. To this end, we extend and apply a molecular theory that has been successfully used in the past to describe and predict the behavior of pH-responsive polymers. Two main results emerge from the present study: First, the addition of Ca2+ to the bulk solution changes—in a concentration-dependent manner—both the ionization and structural state of the end-tethered polymers, affecting, respectively, the ionic conductivity and physical opening of the nanochannel. Second, in the presence of Ca2+ and under specific nanoconfinement conditions, the grafted channel can exhibit a sensitive response to pH in the transition between closed and open states. We attribute this sensitivity to bistability in the system. Our results also indicate that the polymer layer can undergo a microphase separation when the brush collapses on the nanochannel walls. Taken together, these findings suggest the possibility of designing nanogates that can respond to marginal changes in pH or multivalent ion concentration. Such nanodevices may be used as logic gates or for any application that requires a sensitive control over the ions, molecules, or nanoparticles flowing through them.

scholarly journals Smart Composite Hydrogels with pH-Responsiveness and Electrical Conductivity for Flexible Sensors and Logic Gates

Polymers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1564 ◽  
Author(s):  
Tong Wang ◽  
Xuan Zhang ◽  
Zichao Wang ◽  
Xiuzhong Zhu ◽  
Jie Liu ◽  
...  
Keyword(s):  
Environmental Changes ◽  
Logic Gates ◽  
Body Motion ◽  
Smart Composite ◽  
Stimuli Responsive ◽  
Ph Responsive ◽  
Flexible Sensors ◽  
Intelligent Analysis ◽  
Wide Range ◽  
Conductive Hydrogels

Stimuli-responsive conductive hydrogels have a wide range of applications due to their intelligent sensing of external environmental changes, which are important for smart switches, soft robotics, and flexible sensors. However, designing stimuli-responsive conductive hydrogels with logical operation, such as smart switches, remains a challenge. In this study, we synthesized pH-responsive conductive hydrogels, based on the copolymer network of acrylic acid and hydroxyethyl acrylate doped with graphene oxide. Using the good flexibility and conductivity of these hydrogels, we prepared a flexible sensor that can realize the intelligent analysis of human body motion signals. Moreover, the pH-responsive conductive hydrogels were integrated with temperature-responsive conductive hydrogels to develop logic gates with sensing, analysis, and driving functions, which realized the intellectualization of conductive hydrogels.

scholarly journals S-PRG Filler Eluate Induces Oxidative Stress in Oral Microorganism: Suppression of Growth and Pathogenicity, and Possible Clinical Application

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 816
Author(s):  
Yu Kono ◽  
Muneaki Tamura ◽  
Marni E. Cueno ◽  
Morio Tonogi ◽  
Kenichi Imai
Keyword(s):  
Oxidative Stress ◽  
Bacterial Flora ◽  
Oral Care ◽  
Oral Bacteria ◽  
Ion Concentration ◽  
Dependent Manner ◽  
Bacterial Cells ◽  
Oral Diseases ◽  
Concentration Dependent Manner ◽  
Culture Growth

Controlling the oral microbial flora is putatively thought to prevent not only oral diseases, but also systemic diseases caused by oral diseases. This study establishes the antibacterial effect of the novel bioactive substance “S-PRG filler” on oral bacteria. We examined the state of oxidative stress caused by the six types of ions released in eluate from the S-PRG filler in oral bacterial cells. Moreover, we investigated the effects of these ions on the growth and pathogenicity of Gram-positive and Gram-negative bacteria. We found that the released ions affected SOD amount and hydrogen peroxide in bacterial cells insinuating oxidative stress occurrence. In bacterial culture, growth inhibition was observed depending on the ion concentration in the medium. Additionally, released ions suppressed Streptococcus mutans adhesion to hydroxyapatite, S. oralis neuraminidase activity, and Porphyromonas gingivalis hemagglutination and gingipain activity in a concentration-dependent manner. From these results, it was suggested that the ions released from the S-PRG filler may suppress the growth and pathogenicity of the oral bacterial flora. This bioactive material is potentially useful to prevent the onset of diseases inside and outside of the oral cavity, which in turn may have possible applications for oral care and QOL improvement.

scholarly journals pH-Responsive Redox Nanoparticles Protect SH-SY5Y Cells at Lowered pH in a Cellular Model of Parkinson’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 543
Author(s):  
Monika Pichla ◽  
Grzegorz Bartosz ◽  
Ireneusz Stefaniuk ◽  
Izabela Sadowska-Bartosz
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dependent Manner ◽  
Cellular Model ◽  
Ph Responsive ◽  
Mitochondrial Potential ◽  
Concentration Dependent Manner ◽  
Mitochondrial Mass ◽  
Promising Tool ◽  
6 Hydroxydopamine

The damage to SH-SY5Y cells by 6-hydroxydopamine (6-OHDA) is an established cellular model of Parkinson’s disease (PD). Redox nanoparticles are a promising tool for therapy, including neurodegenerative diseases. As pH of the brain tissue at sites affected by PD is lowered down to 6.5, we studied the effect of pH-responsive redox nanoparticles (poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)aminomethylstyrene]), which change their structure in a pH-dependent manner and become active below pH 7 (NRNPs pH), on the viability of SH-SY5Y cells treated with 6-OHDA at pH 6.5 and 7.4. Pretreatment of the cells with NRNPs pH (15–75 μM) prior to the 6-OHDA treatment increased their survival in a concentration-dependent manner at pH 6.5, but not at pH 7.4. Among several parameters studied (ATP and GSH content, the level of reactive oxygen species, mitochondrial potential, mitochondrial mass), only the mitochondrial mass was dose-dependently protected by NRNPs pH at pH 6.5, but not at pH 7.4. These results indicate that the action of NRNPs pH on mitochondria underlies their protective effect in this cellular model of PD. These results may have potential importance for future applications of NRNPs pH in preclinical and perhaps clinical studies.

scholarly journals Gentamycin inhibition of kcl-induced contractions of myometrium isolated from non-pregnant and pregnant cows

2012 ◽  
Vol 49 (No. 11) ◽  
pp. 401-405
Author(s):  
H. Ocal ◽  
M. Yuksel ◽  
A. Ayar
Keyword(s):  
Isometric Force ◽  
In Vitro Study ◽  
Displacement Transducer ◽  
Ion Concentration ◽  
Rank Test ◽  
Organ Bath ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Signed Rank Test

The aim of this study was to investigate the effects of gentamycin on KCl-induced contractions of myometrium isolated from both non-pregnant and pregnant cows. Myometrial strips were isolated from non-pregnant and pregnant cows and suspended in a jacketed organ bath filled with Krebs&rsquo; solution at 37&deg;C (pH 7.4) continuously bubbled with 95% oxygen and 5% carbon dioxide; isometric contractions were recorded using an isometric force displacement transducer. After manifestation of spontaneous contractions, KCl (60 mM) was applied to the bath and the effects of gentamycin (300 &micro;M, 600 &micro;M) on the amplitude (g) and frequency of KCl-induced contractions were evaluated in 10-minute intervals. Data were statistically analysed using Student&rsquo;s t-test and Wilcoxon signed-rank test. Gentamycin inhibited the frequency and amplitude of KCl-induced contractions in a concentration dependent manner. At 300 &micro;M and 600 &micro;M, gentamycin significantly inhibited the amplitude and reduced the frequency of contractions of myometrium isolated from both pregnant and non-pregnant cows. However, an increase in the extracellular Ca<sup>+</sup> ion concentration virtually reversed this blockade. The results of this in vitro study indicate that gentamycin inhibits KCl-induced contractions of myometrium isolated from both non-pregnant and pregnant cows.

EFFECTS OF DILAZEP ON CYTOPLASMIC CALCIUM ION CONCENTRATION AND ARACHIDONIC ACID METABOLISM IN HUMAN PLATELETS AND NEUTROPHILS.

1987 ◽  
Author(s):  
M Okuma ◽  
K Kanaji ◽  
S Sensaki ◽  
H Uchino
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Calcium Ionophore ◽  
Leukotriene B4 ◽  
Human Platelets ◽  
Ion Concentration ◽  
Antiplatelet Drug ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Concentration Dependent Manner

We studied effects of dilazep(DZ), an antiplatelet drug, on the cytoplasmic Ca2+ concentration ([Ca2+]-i) and arachidonic acid (AA) metabolism in human platelets and neutrophils. [Ca2+]i of aequor-in-loaded platelets was estimated by using the platelet ionized calcium aggregometer. AA metabolism was studied by the determination of AA metabolites including hydroxyheptadecatrienoic acid (HHT), hydroxyeicosatetraenoic acid (HETE) and leukotriene B4 (LTB4) by reversed-phase high-performance liquid chromatography. When aequorin-loaded platelets were preincubated with DZ (0−0.5 mM) for 1 min at 37°C, both platelet aggregation and [Ca2+]i elevation induced by thrombin, AA and collagen were inhibited by DZ in a concentration dependent manner, while only aggregation was inhibited after stimulation by the calcium ionophore A23187 (1 yM). Both influx and release of Ca2+ into platelet cytoplasm induced by thrombin or AA were inhibited by DZ, while neither of them was affected when induced by A23187. The production of HHT and 12-HETE by the reaction of 100 yM AA with platelets preincubated with DZ (0−1 mM) was not inhibited, whereas their production by throirfbin (10 u/ml) was remarkably inhibited by DZ in a concentration dependent manner. When DZ (0−0.3 mM)-treated neutrophils were incubated with 5 μM A23187 in the presence or absence of 20 μM AA, the production of LTB4 and 5-HETE was increased by DZ in the presence of AA, whereas their production was inhibited by DZ in its absence. When platelet/neutrophil mixtures preincubated with DZ (0−0.3 mM) and cytochalasin B were stimulated by thrombin (5 u/ml) in the presence of FMLP, DZ inhibited LTB4 production in a concentration dependent manner, while 5S,12S-diHETE synthesis was enhanced by lower concentrations of DZ and inhibited by its higher concentrations (> 0.1 mM).Thus, DZ inhibits platelet aggregation induced by any agonist including A23183, while [Ca2+]i elevation is inhibited by the drug only when it is induced by the receptor-mediated agonist. Furthermore, it was suggested that AA liberation from phospholipids in platelets and neutrophils was inhibited by DZ, leading to reduced production of all endogenous AA metabolites by these cells after appropriate stimulation, although lipoxygenase metabolites of liberated or exogenous AA could be increased.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

Neutrophil Elastase Potentiates Cathepsin G-lnduced Platelet Activation

1992 ◽  
Vol 68 (05) ◽  
pp. 570-576 ◽  
Author(s):  
Mary A Selak
Keyword(s):  
Neutrophil Elastase ◽  
Cell Activation ◽  
Thromboxane A2 ◽  
Creatine Phosphate ◽  
Dense Granule ◽  
Cathepsin G ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Low Concentrations ◽  
High Concentrations

SummaryWe have previously demonstrated that human neutrophil cathepsin G is a strong platelet agonist that binds to a specific receptor. This work describes the effect of neutrophil elastase on cathepsin G-induced platelet responses. While platelets were not activated by high concentrations of neutrophil elastase by itself, elastase enhanced aggregation, secretion and calcium mobilization induced by low concentrations of cathepsin G. Platelet aggregation and secretion were potentiated in a concentration-dependent manner by neutrophil elastase with maximal responses observable at 200 nM. Enhancement was observed when elastase was preincubated with platelets for time intervals of 10–60 s prior to addition of a low concentration of cathepsin G and required catalytically-active elastase since phenylmethanesulphonyl fluoride-inhibited enzyme failed to potentiate cell activation. Neutrophil elastase potentiation of platelet responses induced by low concentrations of cathepsin G was markedly inhibited by creatine phosphate/creatine phosphokinase and/or indomethacin, indicating that the synergism between elastase and cathepsin G required the participation of ADP and thromboxane A2. On the other hand, platelet responses were not attenuated by the PAF antagonist BN 52021, signifying that PAF-acether did not play a role in elastase potentiation. At higher concentrations porcine pancreatic elastase exhibits similar effects to neutrophil elastase, demonstrating that the effect of elastase was not unique to the neutrophil protease. While neutrophil elastase failed to alter the ability of cathepsin G to hydrolyze a synthetic chromogenic substrate, preincubation of platelets with elastase increased the apparent affinity of cathepsin G binding to platelets. In contrast to their effect on cathepsin G-induced platelet responses, neither neutrophil nor pancreatic elasatse potentiated aggregation or dense granule release initiated by ADP, PAF-acether, arachidonic acid or U46619, a thromboxane A2 mimetic. Moreover, unlike its effect on cathepsin G, neutrophil elastase inhibited thrombin-induced responses. The current observations demonstrate that elastase can potentiate platelet responses mediated by low concentrations of cathepsin G, suggesting that both enzymes may function synergistically to activate platelets under conditions where neutrophil degranulation occurs.

Sign in / Sign up

Export Citation Format

Share Document