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Protein phosphorylation is a common and essential post-translational modification that affects biochemical properties and regulates biological activities. Phosphorylation is particularly common for intrinsically disordered proteins and can significantly modulate their function and potential to interact with binding partners. To understand the biophysical origins of how phosphorylation of disordered proteins influences their function, it is valuable to investigate how the modifications lead to changes in their conformational ensembles.

Mast cells mediate their immuno- and neuro-modulatory effects by releasing granules containing bioactive substances. Phosphatidylinositol 4,5-bisphosphate (PIP2), enriched at the plasma membrane (PM), is a key signaling lipid involved in numerous physiological functions including the calcium entry needed for antigen stimulated mast cell degranulation. However, functional nanoscale PIP2 clustering and dynamics have not been previously investigated in immune cells. Using the pleckstrin homology domain from PLCδ (PH) tagged with photoswitchable fluorescent protein Dendra2, clustering was revealed in the mast cell model RBL-2H3, both fixed and live.

Microtubules are essential cytoskeletal components with a broad range of functions in which the structure and dynamics of their plus-end tips play critical roles. Existing mechanistic models explain the tips curving dynamics in different ways: the allosteric model suggests that GTP hydrolysis induces conformational changes in tubulin subunits that destabilize the lattice, leading to protofilament curving and depolymerization, while the lattice model posits that GTP hydrolysis directly destabilizes the microtubule lattice .

The coronavirus main protease (MPro) plays a pivotal role in viral replication and is the target of several antivirals against SARS-CoV-2. In some species, CRCs of MPro enzymatic activity can exhibit biphasic behavior in which low ligand concentrations activate the enzyme whereas higher ones inhibit it. While this behavior has been attributed to ligand-induced dimerization, quantitative enzyme kinetics models have not been fit to it. Here, we develop a kinetic model integrating dimerization and ligand binding.

Many transcription factors regulate DNA accessibility and gene expression by recognizing post-translational modifications on histone tails within nucleosomes. These interactions are often studied in vitro using short peptide mimics of histone tails, which may overlook conformational changes that occur in the full nucleosomal context. Here, we employ molecular dynamics simulations to investigate the binding dynamics of the PHD finger and bromodomain of BPTF, both in solution and bound to either a histone H3 peptide or a full nucleosome.

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.