Fully atomistic molecular dynamics modeling of photoswitchable azo-PC lipid bilayers: structure, mechanical properties, and drug permeation.

Phospholipid based vesicles called liposomes are commonly used as packaging in advanced drug delivery applications. Stimuli-responsive liposomes have been designed to release their contents under certain conditions, for example through heating or illumination. However, in the case of photosensitive liposomes based on azo-PC, namely phosphatidylcholine lipids with azobenzene incorporated into one of the two lipid tails, the release mechanism is not known.

TEMPO-conjugated tobacco mosaic virus as a magnetic resonance imaging contrast agent for detection of superoxide production in the inflamed liver.

Superoxide, an anionic dioxygen molecule, plays a crucial role in redox regulation within the body but is implicated in various pathological conditions when produced excessively. Efforts to develop superoxide detection strategies have led to the exploration of organic-based contrast agents for magnetic resonance imaging (MRI). This study compares the effectiveness of two such agents, nTMV-TEMPO and kTMV-TEMPO, for detecting superoxide in a mouse liver model with lipopolysaccharide (LPS)-induced inflammation.

Self-assembly of a fluorescent virus-like particle for imaging in tissues with high autofluorescence.

Virus-like particles (VLPs) are engineered nanoparticles that mimic the properties of viruses-like high tolerance to heat and proteases-but lack a viral genome, making them non-infectious. They are easily modified chemically and genetically, making them useful in drug delivery, enhancing vaccine efficacy, gene delivery, and cancer immunotherapy. One such VLP is Qβ, which has an affinity towards an RNA hairpin structure found in its viral RNA that drives the self-assembly of the capsid.

The Stiffest and Strongest Predicted Material: C N Atomic Chains Approach the Theoretical Limits.

Though linear atomic chains exhibit extreme properties, it is presently unclear how these properties can be maximized by the choice of elemental composition. Considering that boron, carbon, and nitrogen can form high modulus and high strength atomic chains, here an algorithm is developed to construct 143 possible atomic chains of these elements with 6 or fewer atoms in the primitive cell and explore their stabilities and mechanical properties by first-principles calculations. It is found that the gravimetric modulus (1032 GPa g cm ) and strength (108 GPa g cm ) of the C N chain significantly exceed those of any known material, including the previously stiffest predicted material (C chain, 945 GPa g cm ) and the previously strongest predicted material (BC chain, 92 GPa g cm ), and also approach the theoretical limits of gravimetric modulus (1036 GPa g cm ) and strength (130 GPa g cm ).

Optical control of neuronal activities with photoswitchable nanovesicles.

Precise modulation of neuronal activity by neuroactive molecules is essential for understanding brain circuits and behavior. However, tools for highly controllable molecular release are lacking. Here, we developed a photoswitchable nanovesicle with azobenzene-containing phosphatidylcholine (azo-PC), coined 'azosome', for neuromodulation.

Exogenous Protein Delivery of Ionic Liquid-Mediated HMGB1 Coating on Titanium Implants.

Strategies for modifying titanium (Ti) implant surfaces are becoming increasingly popular to enhance osseointegration during acute and inflammatory healing stages. In this study, two dicationic imidazolium-based ionic liquids (IonLs) containing phenylalanine and methionine anions (IonL-Phe(1,10-bis(3-methylimidazolium-1-yl)decane diphenylalanine) and IonL-Met(1,10-bis(3-methylimidazolium-1-yl)decane dimethionine)) were investigated to stably deliver exogenous proteins on Ti to promote osseointegration. The protein selected for this study is High-Mobility Group Box 1 (HMGB1), which recruits inflammatory and mesenchymal stem cells to the implantation site, contributing to healing.

Curvature and temperature-dependent thermal interface conductance between nanoscale gold and water.

Plasmonic gold nanoparticles (AuNPs) can convert laser irradiation into thermal energy for a variety of applications. Although heat transfer through the AuNP-water interface is considered an essential part of the plasmonic heating process, there is a lack of mechanistic understanding of how interface curvature and the heating itself impact interfacial heat transfer. Here, we report atomistic molecular dynamics simulations that investigate heat transfer through nanoscale gold-water interfaces.

Biophysical and characterization of NrtA: a protein-based host for aqueous nitrate and nitrite recognition.

Nitrate and nitrite are key components of the global nitrogen cycle. As such, Nature has evolved proteins as biological supramolecular hosts for the recognition, translocation, and transformation of both nitrate and nitrite. To understand the supramolecular principles that govern these anion-protein interactions, here, we employ a hybrid biophysical and approach to characterize the thermodynamic properties and protein dynamics of NrtA from the cyanobacterium for the recognition of nitrate and nitrite.

Molecular-Level Understanding of the Influence of Ions and Water on HMGB1 Adsorption Induced by Surface Hydroxylation of Titanium Implants.

Due to its excellent chemical and mechanical properties, titanium has become the material of choice for orthopedic and dental implants to promote rehabilitation via bone anchorage and osseointegration. Titanium osseointegration is partially related to its capability to form a TiO surface layer and its ability to interact with key endogenous proteins immediately upon implantation, establishing the first bone-biomaterial interface. Surgical trauma caused by implantation results in the release of high-mobility group box 1 (HMGB1) protein, which is a prototypic DAMP (damage-associated molecular pattern) with multiple roles in inflammation and tissue healing.

An activity-based fluorescent sensor for the detection of the phenol sulfotransferase SULT1A1 in living cells.

Human phenol sulfotransferases mediate the transfer of a sulfuryl moiety from the activated sulfate donor PAPS to hydroxy-containing substrates, altering substrate solubility and charge to affect phase II metabolism and cell signaling. Here, we present the development, computational modeling, enzymology, and biological application of STS-3, an activity-based fluorescent sensor for the SULT1A1 isoform.

Molecular Dynamics Simulations of Water Condensation on Surfaces with Tunable Wettability.

Water condensation plays a major role in a wide range of industrial applications. Over the past few years, many studies have shown interest in designing surfaces with enhanced water condensation and removal properties. It is well known that heterogeneous nucleation outperforms homogeneous nucleation in the condensation process.

Supramolecular and biomacromolecular enhancement of metal-free magnetic resonance imaging contrast agents.

Many contrast agents for magnetic resonance imaging are based on gadolinium, however side effects limit their use in some patients. Organic radical contrast agents (ORCAs) are potential alternatives, but are reduced rapidly in physiological conditions and have low relaxivities as single molecule contrast agents. Herein, we use a supramolecular strategy where cucurbit[8]uril binds with nanomolar affinities to ORCAs and protects them against biological reductants to create a stable radical .

Transient Photoinactivation of Cell Membrane Protein Activity without Genetic Modification by Molecular Hyperthermia.

Precise manipulation of protein activity in living systems has broad applications in biomedical sciences. However, it is challenging to use light to manipulate protein activity in living systems without genetic modification. Here, we report a technique to optically switch off protein activity in living cells with high spatiotemporal resolution, referred to as molecular hyperthermia (MH).

Non-Arrhenius Reaction-Diffusion Kinetics for Protein Inactivation over a Large Temperature Range.

Understanding protein folding and unfolding has been a long-standing fundamental question and has important applications in manipulating protein activity in biological systems. Experimental investigations of protein unfolding have been predominately conducted by small temperature perturbations (e.g.

Site-Selective Nucleation and Size Control of Gold Nanoparticle Photothermal Antennae on the Pore Structures of a Virus.

In this Article, we show that the surface of the bacteriophage Qβ is equipped with natural ligands for the synthesis of small gold nanoparticles (AuNPs). By exploiting disulfides in the protein secondary structure and the geometry formed from the capsid quaternary structure, we find that we can produce regularly arrayed patterns of ∼6 nm AuNPs across the surface of the virus-like particle. Experimental and computational analyses provide insight into the formation and stability of this composite.

Hydrophilic directional slippery rough surfaces for water harvesting.

Multifunctional surfaces that are favorable for both droplet nucleation and removal are highly desirable for water harvesting applications but are rare. Inspired by the unique functions of pitcher plants and rice leaves, we present a hydrophilic directional slippery rough surface (SRS) that is capable of rapidly nucleating and removing water droplets. Our surfaces consist of nanotextured directional microgrooves in which the nanotextures alone are infused with hydrophilic liquid lubricant.

Investigation of Controlled Growth of Metal-Organic Frameworks on Anisotropic Virus Particles.

Biomimetic mineralization with metal-organic frameworks (MOF), typically zeolitic imidazolate framework-8 (ZIF-8), is an emerging strategy to protect sensitive biological substances against denaturing environmental stressors such as heat and proteolytic agents. Additionally, this same biomimetic mineralization process has the potential of being used to create distinct core-shell architectures using genetically or chemically modified viral nanoparticles. Despite the proliferation of examples for ZIF-8 growth on biological or proteinaceous substrates, systematic studies of these processes are few and far between.

Molecular Hyperthermia: Spatiotemporal Protein Unfolding and Inactivation by Nanosecond Plasmonic Heating.

Spatiotemporal control of protein structure and activity in biological systems has important and broad implications in biomedical sciences as evidenced by recent advances in optogenetic approaches. Here, this study demonstrates that nanosecond pulsed laser heating of gold nanoparticles (GNP) leads to an ultrahigh and ultrashort temperature increase, coined as "molecular hyperthermia", which causes selective unfolding and inactivation of proteins adjacent to the GNP. Protein inactivation is highly dependent on both laser pulse energy and GNP size, and has a well-defined impact zone in the nanometer scale.

Computational and Experimental Studies on the Effects of Monomer Planarity on Covalent Organic Framework Formation.

We report the synthesis of one new boronate ester-based covalent organic framework (COF) and two new covalent organic polymers (COPs) made with fluoranthene-containing monomers and hexahydroxytriphenylene. The structure of the monomer heavily influences whether this material forms a highly ordered mesoporous material (COF) or an amorphous, microporous material (COP). The synthesis of the fluoranthene monomers was carried out using a divergent strategy that allows for systematic structural variation and the ability to conduct a careful structure-function study.

Nested sampling of isobaric phase space for the direct evaluation of the isothermal-isobaric partition function of atomic systems.

Nested Sampling (NS) is a powerful athermal statistical mechanical sampling technique that directly calculates the partition function, and hence gives access to all thermodynamic quantities in absolute terms, including absolute free energies and absolute entropies. NS has been used predominately to compute the canonical (NVT) partition function. Although NS has recently been used to obtain the isothermal-isobaric (NPT) partition function of the hard sphere model, a general approach to the computation of the NPT partition function has yet to be developed.

Contribution of fluorophore dynamics and solvation to resonant energy transfer in protein-DNA complexes: a molecular-dynamics study.

In Förster resonance energy transfer (FRET) experiments, extracting accurate structural information about macromolecules depends on knowing the positions and orientations of donor and acceptor fluorophores. Several approaches have been employed to reduce uncertainties in quantitative FRET distance measurements. Fluorophore-position distributions can be estimated by surface accessibility (SA) calculations, which compute the region of space explored by the fluorophore within a static macromolecular structure.

Nested sampling in the canonical ensemble: direct calculation of the partition function from NVT trajectories.

Nested sampling has emerged as a powerful sampling technique to directly compute the partition function of a realistic molecular system. However, it does so with a non-standard sampling of phase space, which excludes the use of molecular dynamics simulations. Here we show how to use the standard canonical (NVT) sampling of phase space to directly compute the partition function.

A guiding potential method for evaluating the bending rigidity of tensionless lipid membranes from molecular simulation.

A new method is proposed to estimate the bending rigidity of lipid membranes from molecular dynamics simulations. An external cylindrical guiding potential is used to impose a sinusoidal deformation to a planar membrane. The bending rigidity is obtained from the mean force acting on the cylinder by calibrating against a discretized Helfrich model that accounts for thermal fluctuations of the membrane surface.

Adaptive multiscale molecular dynamics of macromolecular fluids.

Until now, adaptive atomistic-coarse-grain (A/CG) molecular dynamics simulations have had very limited applicability because the on-the-fly CG → A transformation is problematic for all but those molecules whose CG representation consists of a single particle. Here, we solve this problem by combining a transitional healing region with a rotational dynamics of rigid atomistic fragments in the CG region. Error control is obtained by analysis of the A ↔ CG energy flow.