Articles Online Now

Dimethyl sulfoxide (DMSO) is a polar aprotic solvent used in a wide range of applications, including uses as a drug and in drug delivery, as a solvent for fluorescence dyes, and in enzymatic reactions that process DNA. Consequently, many assays contain low concentrations (≤ 10%) of DMSO. While it is well known that DMSO lowers the melting temperature of DNA, its effects on DNA conformations and mechanical properties below the melting temperature are unclear. Here we use complementary single-molecule techniques to probe DNA in the presence of 0-60% DMSO.

During early embryo development, cell division is highly organized and synchronized. Understanding the mechanical properties of embryonic cells as a material is crucial for elucidating the physical mechanism underlying embryogenesis. Previous studies on developing embryos using atomic force microscopy (AFM) revealed that single cells of ascidian embryos in the cleavage stage stiffened and softened during cell division. However, how embryonic cells, as a compliant material, exhibit viscoelastic properties during the cell cycle remains poorly characterized.

Ultrasound neuromodulation is a rapidly developing tool for non-invasive control of brain activity. An in vitro model recapitulating the effects of ultrasound on neural tissue in vivo would be extremely valuable in guiding the development of this tool for optimal implementation. Yet, there are relatively few studies of ultrasound on neural activity in vitro. Here we describe our attempts to measure neuromodulatory outcomes using local field potential measurements in two in vitro models of hippocampal activity.

Cardiac contraction is achieved through cyclic cross-bridge interactions between overlapping myosin-containing thick filaments and actin-containing thin filaments. This process is powered by ATP hydrolysis by myosin which must be sufficient for maintaining cardiac output. Myocardial ATP concentration is tightly maintained via several mechanisms. However, in decompensated end-stage heart failure, these mechanisms fail, resulting in depressed myocardial ATP levels, impaired cross-bridge kinetics, and reduced cardiac output.

In order to understand the structure-function relationships of proteins, it is important to study their dynamics under physiological conditions. The advent of X-ray free electron lasers has made it possible to obtain the three-dimensional structures of proteins and their reaction intermediates at room temperature. However, these experiments are very demanding and require extensive planning. Here, we demonstrate that time-resolved infrared difference spectroscopy using quantum cascade lasers is a powerful tool for studying the dynamics of protein conformational changes.

Lipopolysaccharides (LPS) are essential components of the outer membranes of Gram-negative bacteria, playing a crucial role in antimicrobial resistance, virulence, and the host’s immune response. Self-assembled particles displaying LPS are essential for biophysical studies addressing the behaviour of bacterial surfaces under specific biomimetic conditions. Styrene-maleic acid (SMA) copolymers were employed to form LPS nanoparticles, either from extracted LPS or directly from purified outer membranes.

Retinal rod photoreceptors generate reproducible quantal responses enabling them to "count" single photons. Interestingly, in mammalian rods, one photoisomerization in several hundred elicits an aberrant response that is larger than normal and persists for a variable period lasting up to tens of seconds. Although rare, aberrant responses influence signaling because many rods converge onto downstream neurons and because "normal" and aberrant single photon responses temporally summate in steady light.

Biological membranes are complex environments whose functions are closely tied to the dynamic interactions between lipids and proteins. Here, we utilize high-pressure NMR of lipid nanodiscs paired with molecular dynamics simulations to elucidate at the atomic scale the allosteric dialog between the lipid bilayer and a model membrane protein, OmpX. We discover that OmpX delays the gelation process by liquefying the annular shell of lipids through hydrophobic and roughness matching processes at the protein surface.

Small angle X-ray scattering (SAXS) of particles in solution informs on the conformational states and assemblies of biological macromolecules (bioSAXS) outside of cryo- and solid-state conditions. In bioSAXS, the SAXS measurement under dilute conditions, is resolution-limited and through an inverse Fourier transform, the measured SAXS intensities directly relates to the physical space occupied by the particles via the P(r)-distribution. Yet, this inverse transform of SAXS data has been historically cast as an ill-posed, ill-conditioned problem requiring an indirect approach.

Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability to infer the folding mechanisms of globular proteins. The one- and two-body evolutionary energy fields at the amino-acid level are mapped to a coarse-grained description of folding, where proteins are divided into contiguous folding elements, commonly referred to as foldons.

Mosquito-borne flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), constitute a significant and escalating public health threat. Elucidating the mechanisms by which these flaviviruses subvert cellular processes through viral protein-host cell interactions provides critical insights into their replication and pathogenicity. Here, we present an analysis based on anisotropy calculation across pixels in raster images to investigate differential protein interactions during nucleocytoplasmic shuttling.

Organelles such as mitochondria have characteristic shapes that are critical to their function. Recent efforts have revealed that the curvature contributions of individual lipid species can be a factor in the generation of membrane shape in these organelles. Inspired by lipidomics data from yeast mitochondrial membranes, we used Martini coarse-grained molecular dynamics simulations to investigate how lipid composition facilitates membrane shaping. We found that increasing lipid saturation increases bending rigidity while reducing the monolayer spontaneous curvature.