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J. Gupta

Publications and source records attributed to J. Gupta.

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Non-universal Impact of Cholesterol on Ionic Liquid-Membrane Interactions

Understanding the role of cholesterol in ionic liquid (IL)-membrane interactions is essential for advancing biomedical applications of ILs, including the development of innovative antimicrobial agents. In this study, we explore the intricate and multifaceted role of cholesterol in modulating IL-membrane interactions, employing a comprehensive suite of biophysical techniques. We systematically examine how IL alkyl chain length and membrane physical state influence the impact of cholesterol on IL-lipid membrane interaction. The incorporation of ILs is shown to increase the area per lipid in both pristine dipalmitoylphosphatidylcholine (DPPC) and DPPC-cholesterol membranes. Cholesterol modulates the impact of ILs on lipid conformation, membrane viscoelasticity, and phase behavior. Small-angle neutron scattering and dynamic light scattering measurements reveal that cholesterol mitigates IL-induced structural perturbations in vesicles. Our isothermal titration calorimetry measurements reveal that the presence of cholesterol significantly weakens the binding of ILs to membranes. Intriguingly, despite this reduced binding affinity, cholesterol-containing membranes demonstrate enhanced permeabilization. This counterintuitive effect is attributed to cholesterol's ordering of lipid membranes, which increases susceptibility to stress and defects. Our results underscore the complex and non-universal interplay between lipid composition, IL alkyl chain length, and membrane phase state. These insights provide a deeper understanding of cholesterol's role in IL-membrane interactions, paving the way for the design of advanced applications of ILs in antimicrobial therapy and drug delivery.

cond-mat.soft

Quantifying Ionic Liquid Affinity and Its Effect on Phospholipid Membrane Structure and Dynamics

In this study, we examine the impact of imidazolium based ILs on the viscoelasticity, dynamics, and phase behavior of two model membrane systems, (i) lipid monolayers and (ii) unilamellar vesicles composed of dipalmitoylphosphatidylcholine (DPPC). Our findings demonstrate that both ILs induce significant disorder in lipid membranes by altering the area per lipid molecule, thereby modulating their viscoelastic properties. ILs with longer alkyl chains show stronger interactions with membranes, causing more pronounced disorder. Fourier transform infrared spectroscopy indicates that IL incorporation shifts the membrane main phase transition to lower temperatures and introduces gauche defects, signifying increased structural disorder. This effect is amplified with longer alkyl chains and higher IL concentrations. Quasielastic neutron scattering studies highlight that ILs markedly enhance the lateral diffusion of lipids within the membrane leaflet, with the extent of enhancement determined by the membrane physical state, IL concentration, and alkyl chain length. The most pronounced acceleration in lateral diffusion occurs in ordered membrane phase with higher concentrations of the longer chain IL. Molecular dynamics simulations corroborate these experimental findings, showing that longer chain ILs extensively disrupt lipid organization, introduce more gauche defects, increase the area per lipid, and consequently enhance lateral diffusion. This increase in lipid fluidity and permeability provides a mechanistic basis for the observed higher toxicity associated with longer chain ILs.

cond-mat.soft

Structural Reorganizations and Nanodomain Emergence in Lipid Membrane Driven by Ionic Liquids

The exceptional physicochemical properties and versatile biological activities of ionic liquids (ILs) have propelled their potential applications in various industries, including pharmaceuticals and green chemistry. However, their widespread use is limited by concerns over toxicity, particularly due to interactions with cell membranes. This study examines the effects of imidazolium-based ILs on the microscopic structure and phase behavior of a model cell membrane composed of zwitterionic dipalmitoylphosphatidylcholine (DPPC) lipid. Small-angle neutron scattering and dynamic light scattering reveal that the shorter chain IL, 1-hexyl-3-methylimidazolium bromide (HMIM[Br]), induces aggregation of DPPC unilamellar vesicles. In contrast, this aggregation is absent with the longer alkyl chain IL, 1-decyl-3-methylimidazolium bromide (DMIM[Br]). Instead, DMIM[Br] incorporation leads to the formation of distinct IL-poor and IL-rich nanodomains within the DPPC membrane, as evidenced by X-ray reflectivity, differential scanning calorimetry, and molecular dynamics simulation. The less evident nanodomain formation with HMIM[Br] underscores the role of hydrophobic interactions between lipid alkyl tails and ILs. Our findings demonstrate that longer alkyl chains in ILs significantly enhance their propensity to form membrane nanodomains and increase membrane permeability, directly correlating with higher cytotoxicity. This crucial link between nanodomains and toxicity provides valuable insights for designing safer, more environmentally friendly ILs, and promoting their use in biomedical applications and sustainable industrial processes.

cond-mat.soft

Lipid Lateral Diffusion: Mechanisms and Modulators

The lateral diffusion of lipids within membrane is of paramount importance, serving as a central mechanism in numerous physiological processes including cell signaling, membrane trafficking, protein activity regulation, and energy transduction pathways. This review offers a comprehensive overview of lateral lipid diffusion in model biomembrane systems explored through the lens of neutron scattering techniques. We examine diverse models of lateral diffusion and explore the various factors influencing this fundamental process in membrane dynamics. Additionally, we offer a thorough summary of how different membrane-active compounds, including drugs, antioxidants, stimulants, and membrane proteins, affect lipid lateral diffusion. Our analysis unveils the intricate interplay between these additives and membranes, shedding light on their dynamic interactions. We elucidate that this interaction is governed by a complex combination of multiple factors including the physical state and charge of the membrane, the concentration of additives, the molecular architecture of the compounds, and their spatial distribution within the membrane. In conclusion, we briefly discuss the future directions and areas requiring further investigation in the realm of lateral lipid diffusion, highlighting the need to study more realistic membrane systems.

cond-mat.soft

The Physics of Antimicrobial Activity of Ionic Liquids

The bactericidal potency of ionic liquids (ILs) is well-established, yet their precise mechanism of action remains elusive. Here, we show evidence that the bactericidal action of ILs primarily involves permeabilizing the bacterial cell membrane. Our findings reveal that ILs exert their effects by directly interacting with the lipid bilayer and enhancing the membrane dynamics. Lateral lipid diffusion is accelerated which in turn augments membrane permeability, ultimately leading to bacterial death. Furthermore, our results establish a significant connection: an increase in the alkyl chain length of ILs correlates with a notable enhancement in both lipid lateral diffusion and antimicrobial potency. This underscores a compelling correlation between membrane dynamics and antimicrobial effectiveness, providing valuable insights for the rational design and optimization of IL-based antimicrobial agents in healthcare applications.

cond-mat.soft

Biceph-Net: A robust and lightweight framework for the diagnosis of Alzheimer's disease using 2D-MRI scans and deep similarity learning

Alzheimer's Disease (AD) is a neurodegenerative disease that is one of the significant causes of death in the elderly population. Many deep learning techniques have been proposed to diagnose AD using Magnetic Resonance Imaging (MRI) scans. Predicting AD using 2D slices extracted from 3D MRI scans is challenging as the inter-slice information gets lost. To this end, we propose a novel and lightweight framework termed 'Biceph-Net' for AD diagnosis using 2D MRI scans that model both the intra-slice and inter-slice information. Biceph-Net has been experimentally shown to perform similar to other Spatio-temporal neural networks while being computationally more efficient. Biceph-Net is also superior in performance compared to vanilla 2D convolutional neural networks (CNN) for AD diagnosis using 2D MRI slices. Biceph-Net also has an inbuilt neighbourhood-based model interpretation feature that can be exploited to understand the classification decision taken by the network. Biceph-Net experimentally achieves a test accuracy of 100% in the classification of Cognitively Normal (CN) vs AD, 98.16% for Mild Cognitive Impairment (MCI) vs AD, and 97.80% for CN vs MCI vs AD.

eess.IV

First Demonstration of a Scintillating Xenon Bubble Chamber for Detecting Dark Matter and Coherent Elastic Neutrino-Nucleus Scattering

A 30-g xenon bubble chamber, operated at Northwestern University in June and November 2016, has for the first time observed simultaneous bubble nucleation and scintillation by nuclear recoils in a superheated liquid. This chamber is instrumented with a CCD camera for near-IR bubble imaging, a solar-blind photomultiplier tube to detect 175-nm xenon scintillation light, and a piezoelectric acoustic transducer to detect the ultrasonic emission from a growing bubble. The time of nucleation determined from the acoustic signal is used to correlate specific scintillation pulses with bubble-nucleating events. We report on data from this chamber for thermodynamic "Seitz" thresholds from 4.2 to 15.0 keV. The observed single- and multiple-bubble rates when exposed to a $^{252}$Cf neutron source indicate that, for an 8.3-keV thermodynamic threshold, the minimum nuclear recoil energy required to nucleate a bubble is $19\pm6$ keV (1$\sigma$ uncertainty). This is consistent with the observed scintillation spectrum for bubble-nucleating events. We see no evidence for bubble nucleation by gamma rays at any of the thresholds studied, setting a 90% C.L. upper limit of $6.3\times10^{-7}$ bubbles per gamma interaction at a 4.2-keV thermodynamic threshold. This indicates stronger gamma discrimination than in CF$_3$I bubble chambers, supporting the hypothesis that scintillation production suppresses bubble nucleation by electron recoils while nuclear recoils nucleate bubbles as usual. These measurements establish the noble-liquid bubble chamber as a promising new technology for the detection of weakly interacting massive particle dark matter and coherent elastic neutrino-nucleus scattering.

physics.ins-det

The origin of switching noise in GaAs/AlGaAs lateral gated devices

We have studied the origin of switching (telegraph) noise at low temperature in lateral quantum structures defined electrostatically in GaAs/AlGaAs heterostructures by surface gates. The noise was measured by monitoring the conductance fluctuations around $e^2/h$ on the first step of a quantum point contact at around 1.2 K. Cooling with a positive bias on the gates dramatically reduces this noise, while an asymmetric bias exacerbates it. We propose a model in which the noise originates from a leakage current of electrons that tunnel through the Schottky barrier under the gate into the doped layer. The key to reducing noise is to keep this barrier opaque under experimental conditions. Bias cooling reduces the density of ionized donors, which builds in an effective negative gate voltage. A smaller negative bias is therefore needed to reach the desired operating point. This suppresses tunnelling from the gate and hence the noise. The reduction in the density of ionized donors also strengthens the barrier to tunneling at a given applied voltage. Support for the model comes from our direct observation of the leakage current into a closed quantum dot, around $10^{-20} \mathrm{A}$ for this device. The current was detected by a neighboring quantum point contact, which showed monotonic steps in time associated with the tunneling of single electrons into the dot. If asymmetric gate voltages are applied, our model suggests that the noise will increase as a consequence of the more negative gate voltage applied to one of the gates to maintain the same device conductance. We observe exactly this behaviour in our experiments.

cond-mat.mes-hall

The influence of the long-lived quantum Hall potential on the characteristics of quantum devices

Novel hysteretic effects are reported in magneto-transport experiments on lateral quantum devices. The effects are characterized by two vastly different relaxation times (minutes and days). It is shown that the observed phenomena are related to long-lived eddy currents. This is confirmed by torsion-balance magnetometry measurements of the same 2-dimensional electron gas (2DEG) material. These observations show that the induced quantum Hall potential at the edges of the 2DEG reservoirs influences transport through the devices, and have important consequences for the magneto-transport of all lateral quantum devices.

cond-mat.mes-hall