Dissecting the Membrane Association Mechanism of Aerolysin Pores at Femtomolar Concentrations Using Water as a Probe.

Aerolysin is a bacterial toxin that forms transmembrane pores at the host plasma membrane and has a narrow internal diameter and great stability. These assets make it a highly promising nanopore for detecting biopolymers such as nucleic acids and peptides. Although much is known about aerolysin from a microbiological and structural perspective, its membrane association and pore-formation mechanism are not yet fully understood.

Dissecting the hydrogen bond network of water: Charge transfer and nuclear quantum effects.

The molecular structure of water is dynamic, with intermolecular hydrogen (H) bond interactions being modified by both electronic charge transfer and nuclear quantum effects (NQEs). Electronic charge transfer and NQEs potentially change under acidic or basic conditions, but such details have not been measured. In this work, we developed correlated vibrational spectroscopy, a symmetry-based method that separates interacting from noninteracting molecules in self- and cross-correlation spectra, giving access to previously inaccessible information.

Dynamic Second Harmonic Imaging of Proton Translocation Through Water Needles in Lipid Membranes.

Proton translocation through lipid membranes is a fundamental process in the field of biology. Several theoretical models have been developed and presented over the years to explain the phenomenon, yet the exact mechanism is still not well understood. Here, we show that proton translocation is directly related to membrane potential fluctuations.

Liposomes and Lipid Droplets Display a Reversal of Charge-Induced Hydration Asymmetry.

The unique properties of water are critical for life. Water molecules have been reported to hydrate cations and anions asymmetrically in bulk water, being a key element in the balance of biochemical interactions. We show here that this behavior extends to charged lipid nanoscale interfaces.

Lysozyme Interaction with Phospholipid Nanodroplets Probed by Sum Frequency Scattering Vibrational Spectroscopy.

When a nanoparticle (NP) is introduced into a biological environment, its identity and interactions are immediately attributed to the dense layer of proteins that quickly covers the particle. The formation of this layer, dubbed the protein corona, is in general a combination of proteins interacting with the surface of the NP and a contest between other proteins for binding sites either at the surface of the NP or upon the dense layer. Despite the importance for surface engineering and drug development, the molecular mechanisms and structure behind interfacial biomolecule action have largely remained elusive.

Charge Gradients around Dendritic Voids Cause Nanoscale Inhomogeneities in Liquid Water.

Water is the matrix of life and serves as a solvent for numerous physical and chemical processes. The origins of the nature of inhomogeneities that exist in liquid water and the time scales over which they occur remains an open question. Here, we report femtosecond elastic second harmonic scattering (fs-ESHS) of liquid water in comparison to an isotropic liquid (CCl) and show that water is indeed a nonuniform liquid.

Ultrasensitive Label-Free Detection of Protein-Membrane Interaction Exemplified by Toxin-Liposome Insertion.

Measuring the high-affinity binding of proteins to liposome membranes remains a challenge. Here, we show an ultrasensitive and direct detection of protein binding to liposome membranes using high throughput second harmonic scattering (SHS). Perfringolysin O (PFO), a pore-forming toxin, with a highly membrane selective insertion into cholesterol-rich membranes is used.

Hyaluronan orders water molecules in its nanoscale extended hydration shells.

Hyaluronan (HA) is an anionic, highly hydrated bio-polyelectrolyte found in the extracellular environment, like the synovial fluid between joints. We explore the extended hydration shell structure of HA in water using femtosecond elastic second-harmonic scattering (fs-ESHS). HA enhances orientational water-water correlations.

Molecular Mechanism for the Interactions of Hofmeister Cations with Macromolecules in Aqueous Solution.

Ion identity and concentration influence the solubility of macromolecules. To date, substantial effort has been focused on obtaining a molecular level understanding of specific effects for anions. By contrast, the role of cations has received significantly less attention and the underlying mechanisms by which cations interact with macromolecules remain more elusive.

Mapping Electrochemical Heterogeneity at Gold Surfaces: A Second Harmonic Imaging Study.

Designing efficient catalysts requires correlating surface structure and local chemical composition with reactivity on length scales from nanometers to tens of microns. While much work has been done on this structure/function correlation on single crystals, comparatively little has been done for catalysts of relevance in applications. Such materials are typically highly heterogeneous and thus require methods that allow mapping of the structure/function relationship during electrochemical conversion.

Self-Assembly at Water Nanodroplet Interfaces Quantified with Nonlinear Light Scattering.

The interfaces of water micro- and nanodroplets drive environmental, medical, catalytic, biological, and chemical biphasic processes. The interfacial droplet structure and electrostatics greatly determine the reactivity and efficiency of these processes. Droplet interfacial properties are elusive and generally inferred from bulk measurements and are therefore anything but exact.

Imaging the Heterogeneity of the Oxygen Evolution Reaction on Gold Electrodes Operando: Activity is Highly Local.

Understanding the mechanism of the oxygen evolution reaction (OER), the oxidative half of electrolytic water splitting, has proven challenging. Perhaps the largest hurdle has been gaining experimental insight into the active site of the electrocatalyst used to facilitate this chemistry. Decades of study have clarified that a range of transition-metal oxides have particularly high catalytic activity for the OER.

Polyelectrolytes induce water-water correlations that result in dramatic viscosity changes and nuclear quantum effects.

Ions interact with water via short-ranged ion-dipole interactions. Recently, an additional unexpected long-ranged interaction was found: The total electric field of ions influences water-water correlations over tens of hydration shells, leading to the Jones Ray effect, a 0.3% surface tension depression.

Transient domains of ordered water induced by divalent ions lead to lipid membrane curvature fluctuations.

Cell membranes are composed of a hydrated lipid bilayer that is molecularly complex and diverse, and the link between molecular hydration structure and membrane macroscopic properties is not well understood, due to a lack of technology that can probe and relate molecular level hydration information to micro- and macroscopic properties. Here, we demonstrate a direct link between lipid hydration structure and macroscopic dynamic curvature fluctuations. Using high-throughput wide-field second harmonic (SH) microscopy, we observe the formation of transient domains of ordered water at the interface of freestanding lipid membranes.

Spatiotemporal Imaging of Water in Operating Voltage-Gated Ion Channels Reveals the Slow Motion of Interfacial Ions.

Ion channels are responsible for numerous physiological functions ranging from transport to chemical and electrical signaling. Although static ion channel structure has been studied following a structural biology approach, spatiotemporal investigation of the dynamic molecular mechanisms of operational ion channels has not been achieved experimentally. In particular, the role of water remains elusive.

Chemistry of Lipid Membranes from Models to Living Systems: A Perspective of Hydration, Surface Potential, Curvature, Confinement and Heterogeneity.

Lipid membranes provide diverse and essential functions in our cells relating to transport, energy harvesting and signaling. This variety of functions is controlled by the molecular architecture, such as the presence of hydrating water, specific chemical compounds and microscopic structures, such as the local membrane curvature, as well as macroscopic properties, such as the fluidity of the membrane. To understand the chemistry of membranes, ideally one needs access to multiple length scales simultaneously, using probes that are noninvasive, label-free and membrane-interface specific.

Membrane-Protein-Hydration Interaction of α-Synuclein with Anionic Vesicles Probed via Angle-Resolved Second-Harmonic Scattering.

Amyloid formation of the protein α-synuclein promotes neurodegeneration in Parkinson's disease. The normal function of α-synuclein includes synaptic vesicle transport and fusion, and the protein binds strongly to negatively charged vesicles in vitro. Here, we demonstrate that nonresonant angle-resolved second-harmonic scattering detects α-synuclein binding to liposomes through changes in water orientational correlations and can thus be used as a high-accuracy and high-throughput label-free probe of protein-liposome interactions.

Hydration mediated interfacial transitions on mixed hydrophobic/hydrophilic nanodroplet interfaces.

Interfacial phase transitions are of fundamental importance for climate, industry, and biological processes. In this work, we observe a hydration mediated surface transition in supercooled oil nanodroplets in aqueous solutions using second harmonic and sum frequency scattering techniques. Hexadecane nanodroplets dispersed in water freeze at a temperature of ∼15 °C below the melting point of the bulk alkane liquid.

Membrane water for probing neuronal membrane potentials and ionic fluxes at the single cell level.

Neurons communicate through electrochemical signaling within a complex network. These signals are composed of changes in membrane potentials and are traditionally measured with the aid of (toxic) fluorescent labels or invasive electrical probes. Here, we demonstrate an improvement in label-free second harmonic neuroimaging sensitivity by ~3 orders of magnitude using a wide-field medium repetition rate illumination.

The Jones-Ray Effect Is Not Caused by Surface-Active Impurities.

Pure aqueous electrolyte solutions display a minimum in surface tension at concentrations of 2 ± 1 mM. This effect has been a source of controversy since it was first reported by Jones and Ray in the 1930s. The Jones-Ray effect has frequently been dismissed as an artifact linked to the presence of surface-active impurities.

Comment on "Water-water correlations in electrolyte solutions probed by hyper-Rayleigh scattering" [J. Chem. Phys. 147, 214505 (2017)].

The work by Shelton [J. Chem. Phys.

Interaction of Oil and Lipids in Freestanding Lipid Bilayer Membranes Studied with Label-Free High-Throughput Wide-Field Second-Harmonic Microscopy.

The interaction of oils and lipids is relevant for membrane biochemistry since the cell uses bilayer membranes, lipid droplets, and oily substances in its metabolic cycle. In addition, a variety of model lipid membrane systems, such as freestanding horizontal membranes and droplet interface bilayers, are made using oil to facilitate membrane monolayer apposition. We characterize the behavior of excess oil inside horizontal freestanding lipid bilayers using different oils, focusing on hexadecane and squalene.

Temperature dependence of water-water and ion-water correlations in bulk water and electrolyte solutions probed by femtosecond elastic second harmonic scattering.

The temperature dependence of the femtosecond elastic second harmonic scattering (fs-ESHS) response of bulk light and heavy water and their electrolyte solutions is presented. We observe clear temperature dependent changes in the hydrogen (H)-bond network of water that show a decrease in the orientational order of water with increasing temperature. Although DO has a more structured H-bond network (giving rise to more fs-ESHS intensity), the relative temperature dependence is larger in HO.