Enhanced Photostability and Photoactivity of Ruthenium Polypyridyl-Based Photocatalysts by Covalently Anchoring Onto Reduced Graphene Oxide.

Recentstudies toward finding more efficient ruthenium metalloligands for photocatalysis applications have shown that the derivatives of the linear [Ru(dqp)] (dqp: 2,6-di(quinolin-8-yl)-pyridine) complexes hold significant promise due to their extended emission lifetime in the μs time scale while retaining comparable redox potential, extinction coefficients, and absorption profile in the visible region to [Ru(bpy)] (bpy: 2,2'-bipyridine) and [Ru(tpy)] (tpy: 2,2':6',2″-terpyridine) complexes. Nevertheless, its photostability in aqueous solution needs to be improved for its widespread use in photocatalysis. Carbon-based supports have arisen as potential solutions for improving photostability and photocatalytic activity, yet their effect greatly depends on the interaction of the metal complex with the support.

Evaluation of the passive permeability of antidepressants through pore-suspended lipid bilayer.

Hypothesis: The antidepressant drug imipramine, and its metabolite desipramine show different extents of interaction with, and passive permeation through, cellular membrane models, with the effects depending on the membrane composition. Through multimodal interrogation, we can observe that the drugs have a direct impact on the physicochemical properties of the membrane, that may play a role in their pharmacokinetics.

Experiments: Microcavity pore-suspended lipid bilayers (MSLBs) of four different compositions, each with a different headgroup charge namely; zwitterionic dioleoylphosphatidylcholine (DOPC), mixed DOPC and negatively charged dioleoylphosphatidylglycerol (DOPG) (3:1), mixed DOPC and positively charged dioleoyltrimethylammoniumpropane (DOTAP) (3:1), and with increasing complex composition mimicking blood-brain-barrier (BBB) were prepared on gold and polydimethylsiloxane (PDMS) substrates using a Langmuir-Blodgett-vesicle fusion method.

Leaflet by Leaflet Synergistic Effects of Antimicrobial Peptides on Bacterial and Mammalian Membrane Models.

Antimicrobial peptides (AMPs) offer significant hope in the fight against antibiotic resistance. Operating via a mechanism different from that of antibiotics, they target the microbial membrane and ideally should damage it without impacting mammalian cells. Here, the interactions of two AMPs, magainin 2 and PGLa, and their synergistic effects on bacterial and mammalian membrane models were studied using electrochemical impedance spectroscopy, atomic force microscopy (AFM), and fluorescence correlation spectroscopy.

Galectin-3 Binding to αβ Integrin in Pore Suspended Biomembranes.

Galectin-3 (Gal3) is a β-galactoside binding lectin that mediates many physiological functions, including the binding of cells to the extracellular matrix for which the glycoprotein αβ integrin is of critical importance. The mechanisms by which Gal3 interacts with membranes have not been widely explored to date due to the complexity of cell membranes and the difficulty of integrin reconstitution within model membranes. Herein, to study their interaction, Gal3 and αβ were purified, and the latter reconstituted into pore-suspended lipid bilayers comprised eggPC:eggPA.

Role of phosphatidylserine in amyloid-beta oligomerization at asymmetric phospholipid bilayers.

Amyloid-beta (Aβ) aggregation triggers neurotoxicity and is linked to Alzheimer's disease. Aβ oligomers, rather than extended fibrils, adhere to the cell membrane, causing cell death. Phosphatidylserine (PS), an anionic phospholipid, is prevalent in neuronal membranes (< 20 molar percentage) and, while isolated to the cytoplasmic leaflet of the membrane in healthy cells, its exposure in apoptotic cells and migration to exoplasmic leaflet is triggered by oxidative damage to the membrane.

A cell free biomembrane platform for multimodal study of influenza virus hemagglutinin and for evaluation of entry-inhibitors against hemagglutinin.

Seasonal periodic pandemics and epidemics caused by Influenza A viruses (IAVs) are associated with high morbidity and mortality worldwide. They are frequent and unpredictable in severity so there is a need for biophysical platforms that can be used to provide both mechanistic insights into influenza virulence and its potential treatment by anti-IAV agents. Host membrane viral association through the glycoprotein hemagglutinin (HA) of IAVs is one of the primary steps in infection.

Multimodal Investigation into the Interaction of Quinacrine with Microcavity-Supported Lipid Bilayers.

Quinacrine is a versatile drug that is widely recognized for its antimalarial action through its inhibition of the phospholipase enzyme. It also has antianthelmintic and antiprotozoan activities and is a strong DNA binder that may be used to combat multidrug resistance in cancer. Despite extensive cell-based studies, a detailed understanding of quinacrine's influence on the cell membrane, including permeability, binding, and rearrangement at the molecular level, is lacking.

Microcavity array supported lipid bilayer models of ganglioside - influenza hemagglutinin binding.

The binding of influenza receptor (HA1) to membranes containing different glycosphingolipid receptors was investigated at Microcavity Supported Lipid Bilayers (MSLBs). We observed that HA1 preferentially binds to GD1a but the diffusion coefficient of the associated complex at lipid bilayer is approximately double that of the complexes formed by HA1 GM1 or GM3.

Dimethylaniline functionalised pyrene fluorophores; dual colour pH switching in solution and self-assembled monolayers.

A pyrene charge transfer fluorophore with three ionizable N,N-dimethylaniline moieities was explored as an interfacial pH switch. The parent carboxylate compound and the thiolated derivative were shown by spectroscopy combined with DFT calculation to be successively and reversibly protonated. Protonation leads to progressive decrease of intensity of the 550 nm centered N,N-dimethylaniline to pyrene charge transfer emission which on protonation of the third site, leads to extinction of this transition and evolution of an intense blue (450 nm) pyrene-centered emission.

Microcavity-Supported Lipid Membranes: Versatile Platforms for Building Asymmetric Lipid Bilayers and for Protein Recognition.

Microcavity-supported lipid bilayers (MSLBs) are contact-free membranes suspended across aqueous-filled pores that maintain the lipid bilayer in a highly fluidic state, free from frictional interactions with substrate. Such platforms offer the prospect of liposome-like fluidity with the compositional versatility and addressability of supported lipid bilayers and thus offer a significant opportunity to model membrane asymmetry, protein-membrane interactions, and aggregation at the membrane interface. Herein we evaluate their performance by studying the effect of transmembrane lipid asymmetry on lipid diffusivity, membrane viscosity, and cholera toxin-ganglioside recognition across six symmetric and asymmetric membranes including binary compositions containing both fluid and gel phases, and ternary phase-separated membrane compositions.

Microcavity-Supported Lipid Bilayers; Evaluation of Drug-Lipid Membrane Interactions by Electrochemical Impedance and Fluorescence Correlation Spectroscopy.

Many drugs have intracellular or membrane-associated targets, thus understanding their interaction with the cell membrane is of value in drug development. Cell-free tools used to predict membrane interactions should replicate the molecular organization of the membrane. Microcavity array-supported lipid bilayer (MSLB) platforms are versatile biophysical models of the cell membrane that combine liposome-like membrane fluidity with stability and addressability.

Macromolecular inversion-driven polymer insertion into model lipid bilayer membranes.

Macromolecules of amphiphilic invertible polymers (AIPs) are capable of self-assembly into micellar assemblies of various morphologies in solvents of different polarities. The micellar assemblies in aqueous media are capable of encapsulating poorly aqueous soluble cargo and can undergo inverse conformational change and cargo release in contact with non-polar media, including potentially, cell membranes. Thus, invertible micellar assemblies have significant potential in drug delivery and related domains.

Pathways for creation and annihilation of nanoscale biomembrane domains reveal alpha and beta-toxin nanopore formation processes.

Raft-like functional domains with putative sizes of 20-200 nm and which are evolving dynamically are believed to be the most crucial regions in cellular membranes which determine cell signaling and various functions of cells. While the actual sizes of these domains are believed to vary from cell to cell no direct determination of their sizes and their evolution when cells interact with external agents like toxins and relevant biomolecules exists. Here, we report the first direct determination of the size of these nanoscale regions in model raft-forming biomembranes using the method of super-resolution stimulated emission depletion nanoscopy coupled with fluorescence correlation spectroscopy (STED-FCS).

Unraveling complex nanoscale lipid dynamics in simple model biomembranes: Insights from fluorescence correlation spectroscopy in super-resolution stimulated emission depletion mode.

Dynamic heterogeneity (DH) at nanoscale due to lipid-lipid and/or lipid-protein interactions in cell membranes plays a crucial role in determining a broad range of important cell functions. In cell membranes, the dimensions of these nanodomains have been postulated to be in the order of 10's of nm and transient in nature. While the structural features of membranes have been studied in detail, little is known about their dynamical characteristics due to paucity of techniques which can probe nanoscale phenomena with simultaneous high temporal resolution.

Complex dynamics at the nanoscale in simple biomembranes.

Nature is known to engineer complex compositional and dynamical platforms in biological membranes. Understanding this complex landscape requires techniques to simultaneously detect membrane re-organization and dynamics at the nanoscale. Using super-resolution stimulated emission depletion (STED) microscopy coupled with fluorescence correlation spectroscopy (FCS), we reveal direct experimental evidence of dynamic heterogeneity at the nanoscale in binary phospholipid-cholesterol bilayers.

Regio-selective lipase catalyzed hydrolysis of oxanorbornane-based sugar-like amphiphiles at air-water interface: A polarized FT-IRRAS study.

Interfacial hydrolysis of oxanorbornane-based amphiphile (Triol C16) by Candida rugosa lipase was investigated using real-time polarized Fourier transform-infrared reflection absorption spectroscopy (FT-IRRAS). The kinetics of hydrolysis was studied by analyzing the ester carbonyl ν(CO) stretching vibration band across the two dimensional (2D) array of molecules at the confined interface. In particular, we demonstrate Triol C16 to form Michaelis-Menten type complex, like that of lipid-substrate analogues, where the Triol C16 head group remained accessible to the catalytic triad of the lipase.

Nanoscale dynamics of phospholipids reveals an optimal assembly mechanism of pore-forming proteins in bilayer membranes.

Cell membranes are believed to be highly complex dynamical systems having compositional heterogeneity involving several types of lipids and proteins as the major constituents. This dynamical and compositional heterogeneity is suggested to be critical to the maintenance of active functionality and response to chemical, mechanical, electrical and thermal stresses. However, delineating the various factors responsible for the spatio-temporal response of actual cell membranes to stresses can be quite challenging.

Super-resolution Stimulated Emission Depletion-Fluorescence Correlation Spectroscopy Reveals Nanoscale Membrane Reorganization Induced by Pore-Forming Proteins.

Membrane-protein interactions play a central role in membrane mediated cellular processes ranging from signaling, budding, and fusion, to transport across the cell membrane. Of particular significance is the process of efficient protein olgomerization and transmembrane pore formation on the membrane surface; the primary virulent pathway for the action of antimicrobial peptides and pore forming toxins (PFTs). The suggested nanoscopic length scales and dynamic nature of such membrane lipid-protein interactions makes their detection extremely challenging.

Structure and dynamics of H2O vis-á-vis phenylalanine recognition at a DPPC lipid membrane via interfacial H-bond types: insights from polarized FT-IRRAS and ADMP simulations.

Preferential and enantioselective interactions of L-/D-Phenylalanine (L-Phe and D-Phe) and butoxycarbonyl-protected L-/D-Phenylalanine (LPA and DPA) as guest with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (L-DPPC) as host were tapped by using real time Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS). Polarization-modulated FT-IRRAS of DPPC monolayers above the phenylalanine modified subphases depicted fine structure/conformation differences under considerations of controlled 2D surface pressure. Selective molecular recognition of D-enantiomer over L-enantiomer driven by the DPPC head group via H-bonding and electrostatic interactions was evident spectroscopically.

Anomalous subsurface thermal behavior in tissue mimics upon near infrared irradiation mediated photothermal therapy.

Photothermal therapy using (Near Infrared) NIR region of EM spectrum is a fast emerging technology for cancer therapy. Different types of nanoparticles may be used for enhancing the treatment. Though the treatment protocols are developed based on experience driven estimated temperature increase in the tissue, it is not really known what spatiotemporal thermal behavior in the tissue is.

Establishing the ellipsoidal geometry of a benzoic acid-based amphiphile via dimer switching: insights from intramolecular rotation and facial H-bond torsion.

Soft molecular ellipsoids conceived from 3,4-di(dodecyloxy)benzoic acid (DDBA) amphiphile draw attention to monomer structure design, intramolecular -COOH headgroup twist (ϕ°) and cyclic-acyclic dimer switching through facial H-bond torsion (ψ°). Generically, precipitation in hydrogen bonded systems has been the prime phenomenon once the critical aggregation concentrations were reached in the bulk solution. DDBA was no exception to this generalization.

L-tryptophan-induced electron transport across supported lipid bilayers: an alkyl-chain tilt-angle, and bilayer-symmetry dependence.

Molecular orientation-dependent electron transport across supported 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayers (SLBs) on semiconducting indium tin oxide (ITO) is reported with an aim towards potential nanobiotechnological applications. A bifunctional strategy is adopted to form symmetric and asymmetric bilayers of DPPC that interact with L-tryptophan, and are analyzed by surface manometry and atomic force microscopy. Polarization-dependent real-time Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS) analysis of these SLBs reveals electrostatic, hydrogen-bonding, and cation-π interactions between the polar head groups of the lipid and the indole side chains.

Unraveling tryptophan modulated 2D DPPC lattices: an approach toward stimuli responsiveness of the pulmonary surfactant.

A molecular understanding on the preferential and selective interactions of L-tryptophan, a major component of surfactant proteins, with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) is important in the metabolic cycle of the pulmonary surfactant. In view of this, interfacial signals of interest in real time were tapped with aligned DPPC monolayers over a physiological tryptophan subphase using extremely surface sensitive 2D vibrational spectroscopy. Polarization-modulated and angle dependent Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS) of DPPC monolayers on water and L-tryptophan subphases depicted fine structure/conformation differences in the interaction modes, evidenced from changes in the vibrational band intensities and frequencies under conditions of controlled 2D surface pressure.