The explicit role of interfacial hydration during polyethylene glycol induced lipid fusion: a THz spectroscopic investigation.

While the phenomenon of excipient mediated membrane fusion has been studied widely, the inherent role of interfacial hydration involved in the process has mostly remained unaddressed. Here we report the experimental validation of the fact that PEG-induced membrane fusion is associated with the dehydration of the membrane(s). We explore the explicit hydration behavior at three different lipids (DOPC, POPC and DPPC) membranes with different aliphatic tails as they undergo fusogenic transition in the presence of PEG of average molecular weight of 4000 using THz-FTIR spectroscopy in the frequency window of 1.5-13.5 THz. Dynamic light scattering and electron microscopic measurements confirm the formation of different intermediate steps of the liposomes during the fusion process: bilayer aggregation, destabilization and finally lipid fusion. We observe that membrane hydration follows a systematic trend with the lipid specificity as the fusion process sets in.

Impact of hydrophobicity on local solvation structures and its connection with the global solubilization thermodynamics of amphiphilic molecules.

The relationship between the local solvation structures and global thermodynamics, specifically in the case of amphiphilic molecules, is a complex phenomenon and is not yet fully understood. With the prior knowledge that local solvation structures can impose a significant impact on the overall solvation process, we here combine THz spectroscopic analysis with MD simulations to investigate the impact of the altered hydrophobicity and polarity of amphiphilic solute molecules on the local solvation configurations. We use two water soluble alcohols: ethanol (EtOH) and its fluorinated counterpart, 2,2,2-trifluoroethanol (TFE), as model solutes. Our study is aimed to determine the relative abundance of different hydrogen bonded conformers and to establish a correlation between the spectral signatures (as obtained from THz spectroscopic measurements) and microscopic solute-solvent interactions associated with the local solvation structures (as obtained from MD simulations). Finally, we estimate the possible energetic parameters associated with the alcohol solubilization process. We found that while both the alcohols are completely water soluble, they receive a contrasting solvation energy share in terms of entropy and enthalpy. We understand that these findings are not limited to the specific system studied here but can be broadly extrapolated to other amphiphilic aqueous solutions.

TMDC ternary alloy-based triboelectric nanogenerators with giant photo-induced enhancement.

Multifunctional self-powered energy harvesting devices have attracted significant attention for wearable, portable, IoT and healthcare devices. In this study, we report transition metal dichalcogenide (TMDC) ternary alloy (Mo0.5W0.5S2)-based self-powered photosensitive vertical triboelectric nanogenerator (TENG) devices, where the ternary alloy functions both as a triboelectric layer and as a photoabsorbing material. The scalable synthesis of the highly crystalline Mo0.5W0.5S2 ternary alloy can overcome the limitations of binary TMDCs (MoS2, WS2) by utilizing its superior optical characteristics, enabling this semiconductor-based TENG device to simultaneously exhibit photoelectric and triboelectric properties. Benefiting from visible light absorption, this vertical TENG device generates higher triboelectric outputs and exhibits excellent power harvesting properties under visible light illumination. The open circuit voltage and short circuit currents of the devices under illumination (410 nm, 525 µW cm-2) are enhanced by 62% and 253%, respectively, while in the darkness, a very high photoresponsivity of ∼45.5 V mW-1 (voltage mode) is exhibited, indicating the superior energy harvesting potential under ultralow illumination. Furthermore, the energy harvesting ability from regular human activities and the operation as artificial e-skin expands the multi-functionality of this TENG device, paving a pathway for simultaneous mechanical and photonic energy harvesting with self-powered sensing.

Sugar Molecules Inhibit Insulin Aggregation: A Decisive Role Being Played by the Protein Solvation Energetics.

Insulin plays vital roles in controlling blood sugar level in the human body. However, it sometimes aggregates during the storage, and its efficacy (on the treatment of diabetes II disease) reduces significantly. So, understanding the insulin aggregation could help in long-term storage. Here we investigate the amyloid growth of human insulin protein in the presence of sugar molecules and observe that glucose and sucrose delay the insulin aggregation, the effect being systematically sugar dependent. We then investigate protein hydration during the aggregation process using terahertz spectroscopy, as the hydration plays a pioneering role in maintaining biological systems. Our study infers that the water network changes systematically with protein conformations and solvation entropy-enthalpy balance plays a decisive role in the aggregation process.

Solvation Plays a Key Role in Antioxidant-Mediated Attenuation of Elevated Creatinine Level: An In Vitro Spectroscopic Investigation.

An elevated level of creatinine (CRN) is a mark of kidney ailment, and prolonged retention of such condition could lead to renal failure, associated with severe ischemia. Antioxidants are clinically known to excrete CRN from the body through urine, thereby reducing its level in blood. The molecular mechanism of such an exclusion process is still illusive. As the excretion channel is urine, solvation of the solute is expected to play a pivotal role. Here, we report a detailed time-domain and frequency-domain terahertz (THz) spectroscopic investigation to understand the solvation of CRN in the presence of two model antioxidants, mostly used to treat elevated CRN level: N-Acetyl-l-cysteine (NAC) and ascorbic acid (ASC). FTIR spectroscopy in the mid-infrared region and UV absorption spectroscopy measurements coupled with quantum chemical calculations [at the B3LYP/6-311G++(d,p) level] reveal that both NAC and ASC form HBonded complexes with CRN and rapidly undergo a barrier-less proton transfer process to form creatinium ions. THz measurements provide explicit evidence of the formation of highly solvated complexes compared with bare CRN, which eventually enables its excretion through urine. These observations could provide a foundation for designing more beneficial drugs to resolve kidney diseases..

Superior piezoelectric performance of chemically synthesized transition metal dichalcogenide heterostructures for self-powered flexible piezoelectric nanogenerator.

In addition to the superior electrical and optoelectronic attributes, ultrathin two-dimensional transition metal dichalcogenides (TMDCs) have evoked appreciable attention for their piezoelectric properties. In this study, we report, the piezoelectric characteristics of large area, chemically exfoliated TMDCs and their heterostructures for the first time, as verified by piezoelectric force microscopy measurements. Piezoelectric output voltage response of the MoS2-WSe2heterostructure piezoelectric nanogenerator (PENG) is enhanced by ∼47.5% if compared with WSe2and ∼29% if compared to MoS2PENG, attributed to large band offset induced by heterojunction formation. This allows the scalable fabrication of self-powered energy harvesting PENGs, which can overcome the various shortcomings of complicated synthesis processes, complex fabrication steps, low yield, and poor stability. The fabricated flexible, self-powered MoS2-WSe2heterostructure nanogenerator exhibits piezoelectric output ∼46 mV under a strain of ∼0.66% yielding a power output ∼12.3 nW, which offers better performance than other two-dimensional material based piezoelectric devices and also reveals the ability of bio-mechanical energy harvesting. This cost effective approach to fabricate eco-friendly MoS2-WSe2based fatigue free, superior performance piezoelectric-nanogenerators can be utilized to evolve flexible energy harvesting devices and may also be attractive as a self-powered, smart wearable sensor devices.

Thermo-Resistive Phase Behavior of Trivalent Ion-Induced Microscopic Protein-Rich Phases: Correlating with Ion-Specific Protein Hydration.

Proteins, in the presence of trivalent cations, exhibit intriguing phase behavior which is contrasting compared to mono- and divalent cations. At room temperature (RT), trivalent cations induce microscopic liquid-liquid phase separation (LLPS) in which a protein-rich phase coexists with a dilute phase. The critical solution temperature related phenomena in these complex fluids are well studied; however, such studies have mostly been restricted below the denaturation temperature (TM) of the protein(s) involved. Here, we probe the phase behavior of bovine serum albumin (BSA) incubated at 70 °C (>TM) in the presence of Na+, Mg2+, La3+, Y3+, and Ho3+ ions. BSA in the presence of mono- and bivalent ions forms an intense gel phase at 70 °C; however, the trivalent salts offer remarkable thermal resistivity and retain the fluid LLPS phase. We determine the microscopic phase behavior using differential interference contrast optical microscopy, which shows that the LLPS droplet structures in the M3+ ion-containing protein solutions prevail upon heating, whereas Mg2+ forms composed cross-linking gelation upon thermal incubation. We probe the interior environment of the protein aggregates by ps-resolved fluorescence anisotropy measurements using 8-anilino-1-naphthalenesulfonic acid (ANS) as an extrinsic fluorophore. It reveals that while the LLPS phase retains the rotational time constants upon heating, in the case of gelation, the immediate environment of ANS gets significantly perturbed. We investigate the explicit protein hydration at RT as well as at T > TM using the ATR THz-FTIR (1.5-22.5 THz) spectroscopy technique and found that hydration shows strong ion specificity and correlates the phase transition behavior.

Interfacial Structure and Electrostatics Related to Solute Activity in a Model Anionic-Surfactant/Polymer Self-Assembly.

Polymer/surfactant composites are used in industry as an excipient for water-insoluble solutes. Such enhanced dissolution ability of composite media is related to the spontaneous formation of pre-micellar polymer surfactant aggregates (PS) at a magnitude of order lower than the surfactant critical micelle concentration in water. Combining electrochemical and spectroscopic studies, we investigate the microscopic interfacial structure (i.e., interface electrostatics and surface polarity) of PS formed in composite media. We establish that in a composite system, a mere change in the polymer concentration at a fixed surfactant concentration makes possible to regulate the counter-ion binding ability, surface potential, surface charge density, packing and surface polarity of the PS interface. Our study shows that the higher dissolution of water-insoluble nonionic solutes in composite media is driven by the depressing of surface charge density and polarity of the PS interface. A similar modulation of the PS interface acts as a barrier for the passive relocation of water-soluble charged solutes into the PS pseudo-phase. The time-resolved fluorescence anisotropy study allows us to underline the effect of surface charge modulation on the dynamical aspects of solutes at the PS interface.

Trivalent cation-induced phase separation in proteins: ion specific contribution in hydration also counts.

Multivalent (specifically trivalent) metal ions are known to induce microscopic phase separation (commonly termed as liquid-liquid phase separation (LLPS)) in negatively charged globular proteins even at ambient temperatures, the process being mostly driven by protein charge neutralization followed by aggregation. Recent simulation studies have revealed that such self-aggregation of proteins is entropy driven; however, it is associated with a solvation effect, which could as well be different from the usual notion of hydrophobic hydration. In this contribution we have experimentally probed the explicit change in hydration associated with ion-induced LLPS formation of a globular protein bovine serum albumin (BSA) at ambient temperature using FIR-THz FTIR spectroscopy (50-750 cm-1; 1.5-22.5 THz). We have used ions of different charges: Na+, K+, Ca2+, Mg2+, La3+, Y3+, Ho3+ and Al3+. We found that all the trivalent ions induce LLPS; the formation of large aggregates has been evidenced from dynamic light scattering (DLS) measurements, but without perturbing the protein structure as confirmed from circular dichroism (CD) measurements. From the frequency dependent absorption coefficient (α(ν)) measurements in the THz frequency domain we estimate the various stretching/vibrational modes of water and we found that ions, forming LLPS, produce definite perturbation in the overall hydration, the extent of which is ion specific, invoking the definite role of hydrophilic (electrostatic) hydration of ions in the observed LLPS process.

Addition of cholesterol alters the hydration at the surface of model lipids: a spectroscopic investigation.

Cholesterol is known to modify the phase behavior of model lipid membranes as it makes phospholipid bilayers more structured. Simulation results have shown that the addition of cholesterol allows more bulk-like water to protrude into phospholipid interfaces. However, such claims have not yet been verified experimentally. We have investigated the alteration in the hydrogen bond network structure of water at the surface of two model phospholipids DOPC and DOPG as cholesterol is added into these using ATR-FTIR spectroscopy in the FIR-THz region. Our measurements and analysis led us to probe the collective H-bond network explicitly at the lipid surface. A detailed principal component analysis of the measured data concludes that the water-water H-bond vibration dynamics gets slower at the lipid surface as compared to bulk water, the effect being more prominent in the case of the charged phospholipid, DOPG. However, as cholesterol is added and more bulk-like water protrudes into the liposome interface, the H-bond vibration gets weaker and correspondingly the dynamics gets accelerated.

Nonpolar hydrophobic amino acids tune the enzymatic activity of lysozyme.

We have used five different hydrophobic L-amino acids (Gly, Ala, Val, Leu, Ile) as molecular crowders to investigate their role on the enzymatic activity of lysozyme towards Micrococcus lysodeikticus (M. lys.)cell as substrate. We found that except Ile, all other amino acids show a bell like profile of catalytic efficiency (kcat/Km) with their increasing concentration whereas for Ile, the value is gradually increasing. The trend of activation energy (Ea) is also well correlated with the catalytic efficiency of lysozyme. At low concentration of amino acids, soft interaction predominates whereas at higher concentration range, excluded volume, viscosity, hydrophobicity combinedly decrease the activity of lysozyme.

Molecular Insight into Dye-Surfactant Interaction at Premicellar Concentrations: A Combined Two-Photon Absorption and Molecular Dynamics Simulation Study.

Both electrostatic and hydrophobic interactions play pivotal roles in ligand-surfactant binding interaction, especially for ionic surfactants. While much studies have been reported in the micellar region, less attention has been paid on such interactions at a low (premicellar) surfactant concentration. We here study the interaction between the cationic dye rhodamine 6G (R6G) with surfactants of different charge types: anionic SDS, cationic CTAB, and nonionic Tx 100 using absorption and emission spectroscopy. We identify that R6G forms dimeric aggregates at a premicellar concentration of SDS. Formation of aggregates is also confirmed from classical simulation measurements. CTAB and Tx 100 do not form any such aggregate, presumably owing to unfavorable electrostatic interactions. For a molecular-level understanding, we perform two-photon absorption (TPA) spectroscopy for the same systems. TPA allows us to calculate the two-photon absorption cross section and subsequently the change in the dipole moment (Δµ) between ground and excited states of the dye. We calculate the Δµ and observe that it passes through a maximum at a surfactant concentration half of the critical micelle concentration of SDS. This observation imparts support to earlier quantum mechanical calculation, which infers deviation from the parallel orientation of the dye during surfactant-induced aggregation. We extended our measurements and varied the carbon chain length of the anionic surfactant, and we found that all of them exhibit a maximum in Δµ, while their relative magnitude is dependent on the surfactant carbon chain length.

Excipients Do Regulate Phase Separation in Lysozyme and Thus Also Its Hydration.

While the liquid-liquid phase separation (LLPS) process in proteins has been studied in great detail, it has not been widely explored how the associated protein hydration changes during the process and how crucial its role is in the process itself. In this contribution, we experimentally explore the alteration of lysozyme hydration during its LLPS process using attenuated total reflection (ATR)-FTIR spectroscopy in the THz frequency region (1.5-21 THz). Additionally, we explore the role of excipients (l-arginine, sucrose, bovine albumin (BSA), and ubiquitin (Ubi)) in regulating the process and found that, while sucrose stabilizes the LLPS, BSA inhibits it. The effect of Arg in the LLPS is subtle, and that of Ubi is concentration dependent. We made a detailed analysis of the hydration profile of Lys in the presence of these excipients and observe that a change in hydration in terms of H-bond making/breaking is a definite signature regulating the process.

High-Responsivity Gate-Tunable Ultraviolet-Visible Broadband Phototransistor Based on Graphene-WS2 Mixed-Dimensional (2D-0D) Heterostructure.

Recent progress in the synthesis of highly stable, eco-friendly, cost-effective transition-metal dichalcogenide (TMDC) quantum dots (QDs) with their broadband absorption spectra and wavelength selectivity features have led to their increasing use in broadband photodetectors. With the solution-based processing, we demonstrate a superlarge (∼0.75 mm2), ultraviolet-visible (UV-vis) broadband (365-633 nm) phototransistor made of WS2 QDs-decorated chemical vapor deposited (CVD) graphene as the active channel with extraordinary stability and durability under ambient conditions (without any degradation of photocurrent until 4 months after fabrication). Here, colloidal zero-dimensional (0D) WS2 QDs are used as the photoabsorbing material, and graphene acts as the conducting channel. A high photoresponsivity (3.1 × 102 A/W), moderately high detectivity (∼8.9 × 108 Jones), and low noise equivalent power (∼9.7 × 10-11 W/Hz0.5) are obtained at a low bias voltage (Vds = 1 V) at an illumination of 365 nm with optical power as low as ∼0.8 µW/cm2, which can be further tuned by modulating the gate bias. While comparing the photocurrent between two different morphologies of WS2 [QDs and two-dimensional (2D) nanosheets], a significant enhancement of photocurrent is observed in the case of QD-based devices. Ab initio density functional theory (DFT)-based calculations further support our observation, revealing the role of quantum confinement in enhanced photoresponse. Our work reveals a strategy toward developing a scalable, cost-effective, high-performance hybrid mixed-dimensional (2D-0D) photodetector with graphene-WS2 QDs for next-generation optoelectronic applications.

2D WS2 embedded PVDF nanocomposites for photosensitive piezoelectric nanogenerators with a colossal energy conversion efficiency of ∼25.6.

Benefiting from the advantages of low cost, light weight and mechanical flexibility, piezoelectric nanogenerators have the potential for application in renewable energy harvesting from various unexplored sources. Here, we report the demonstration of the record efficiency of flexible piezoelectric nanogenerators (PENG) using composites of polyvinylidene fluoride (PVDF) and chemically exfoliated tungsten disulfide (WS2) nanosheets, which are found to be strongly photosensitive, making them attractive for self-powered optical devices. The presence of two-dimensional (2D) WS2 nanosheets in the PVDF matrix plays a dual role in enhancing the nucleation of the electroactive ß-phase as well as inducing strong photosensitivity in the nanocomposite. The PVDF-WS2 composed flexible device is able to produce an enormously high output voltage of ∼116 V (for an impact of 105 kPa) and a piezoelectric energy conversion efficiency of ∼25.6%, which is the highest among the reported values for PVDF-2D material based self-poled piezoelectric nanogenerators. This self-poled piezo-phototronic device exhibits strain-dependent photocurrent at zero bias and exhibits a responsivity of 6.98 × 10-3 A W-1 at 0.75% strain under the illumination of 410 nm. The fabricated PENG is also able to harvest energy from routine human activities (finger tapping, writing on paper, mouse clicking, etc.) and movement of human body parts. These results open up a new horizon in piezo-phototronic materials through the realization of photosensitive multifunctional PENGs, which can be scaled up for fabricating compact, high performance, portable and self-powered wearable electronic devices for smart sensor applications.

Correlating solvation with conformational pathways of proteins in alcohol-water mixtures: a THz spectroscopic insight.

Water, being an active participant in most of the biophysical processes, is important to trace how protein solvation changes as its conformation evolves in the presence of solutes or co-solvents. In this study, we investigate how the secondary structures of two diverse proteins - lysozyme and ß-lactoglobulin - change in the aqueous mixtures of two alcohols - ethanol and 2,2,2-trifluoroethanol (TFE) using circular dichroism measurements. We observe that these alcohols change the secondary structures of these proteins and the changes are protein-specific. Subsequently, we measure the collective solvation dynamics of these two proteins both in the absence and in the presence of alcohols by measuring the frequency-dependent absorption coefficient (α(ν)) in the THz (0.1-1.2 THz) frequency domain. The alcohol-water mixtures exhibit a non-ideal behaviour with the highest absorption difference (Δα) obtained at Xalcohol = 0.2. The protein solvation in the presence of the alcohols shows an oscillating behaviour in which Δαprotein changes with Xalcohol. Such an oscillatory behaviour of protein solvation results from a delicate interplay between the protein-water, protein-alcohol and water-alcohol associations. We attempt to correlate the various structural conformations of the proteins with the associated solvation.

Effect of Surfactant Tail Length on the Hydroxypropyl Cellulose-Mediated Premicellar Aggregation of Sodium n-Alkyl Sulfate Surfactants.

Polymer/surfactant composites have emerged as a subject of interest for their diverse applications. The improved solution properties in polymer/surfactant composites have been correlated to the formation of premicellar surfactant aggregate-polymer complexes (PS) at a surfactant concentration well below their critical micelle concentrations. Using different physicochemical and spectroscopic techniques here we have studied PS formed by hydroxypropyl cellulose, a nonionic-biocompatible polymer, and alkyl sulfate surfactants of different tail lengths. Our study shows that an increase in surfactant tail length eases PS formation and enhances PS-induced polymer cross-linking and, correspondingly, solution viscosity. PS consisting of shorter tail surfactants and those with longer tail surfactants differ microscopically as the former offers more polar interior than the later as evidenced from fluorescence measurements. Our study establishes that shorter tail surfactants intend to stay loosely packed inside PS and allow larger water penetration, which creates a relatively polar hydrophobic core compared to the PS with longer tail surfactants. The stronger packing of PS with longer tail surfactants is an outcome of favorable interaction between polymer polar groups and surfactant headgroups, which further creates strongly hydrogen-bonded water in their hydration shell.

Alteration of water absorption in the THz region traces the onset of fibrillation in proteins.

Using terahertz spectroscopy, we established the alteration of the collective hydration of water during the fibrillation process (native → intermediate → fibril) of a model protein bovine serum albumin. This label-free study concludes that water dynamics change systematically with protein conformational changes as it experiences a hydrophobic environment during the initial protein unfolding process, followed by the release of bound water during oligomerization and finally the hydrophobic interior of the fibril.

Connection of large amplitude angular jump motions with temporal heterogeneity in aqueous solutions.

It has now been established that large angular jumps do take place when a rotating water molecule exchanges its hydrogen bond (H-bond) identity. This motion differs from the small angular diffusional steps occurring within short time intervals which define the 'Debye diffusion model' of water dynamics. We intend to investigate whether these two processes do eventually complement each other. In this present investigation the orientational dynamics of water in its mixture with a small hydrophobic molecule 1,2-dimethoxy ethane (DME) is studied microscopically using the all-atom classical molecular dynamics (MD) simulation technique. We found that the reorientational motions of water molecules are governed by continuous making and breaking of intermolecular H-bonds with their partners. We characterise these H-bond reorientation motions with the description of the "large amplitude angular jump model" and explore the coupling between the rotational and translational motions. By following the trajectories of each molecule in the solutions we describe the orientational dynamics of liquid water with a 'continuous time random walk' (CTRW) approach. Finally, we explore the diffusivity distribution through the jump properties of the water molecules, which successfully leads to the inherent transient heterogeneity of the solutions. We observe that the heterogeneity increases with increasing DME content in the mixtures. Our study correlates the coupling between rotational and translational motions of water molecules in the mixtures.

Polyethylene glycols affect electron transfer rate in phenosafranin-DNA complex.

Long distance electron transfer (ET) between small ligands and DNA is a much studied phenomenon and is principally believed to occur through electron (or hole) hopping. Several studies have been carried out in aqueous environments while in real biological milieu the DNA molecules experience a more dense and heterogeneous environment containing otherwise indifferent molecular crowders. It is therefore expected that the ET could get modified in the presence of crowding agent and to investigate that we have made elaborate studies on steady state and time-resolved (picosecond (ps) and femtosecond (fs)-resolved) emission properties of a phenosafranine (PSF) intercalated to calf thymus (CT) DNA in the presence of ethylene glycol (EG) and polyethylene glycols (PEG) of different chain lengths (PEG 200, 400 and 1000). The emission of PSF gets considerably quenched when intercalated to DNA; the quenching is released when PEGs are added into it. The structural integrity of the CT DNA has been established using circular dichroism spectroscopy. CD measurements have evidenced only marginal changes in the DNA structure upon the addition of PEGs. ps-Resolved fluorescence measurements show significant decrease in the contribution of the DNA induced quenched time-constant of PSF upon the addition of PEGs, however, fs-resolved measurements show less noticeable changes in the time constants. Our study shows that the electron hopping rate through the guanine base in DNA core remains unaffected whereas the 'through space' electron transfer process does get affected in the presence of molecular crowders.