Hydration and Antibiofouling Behavior of Zwitterionic Polycarboxybetaine-Grafted Surfaces Studied with Atomistic Simulations.

Fouling-resistant coating materials have important applications in marine industry and biomedicine. Zwitterionic carboxybetaine polymers have demonstrated robust antibiofouling functionalities in experiments. In this work, we performed atomistic molecular dynamics simulations to study the molecular mechanism of hydration and antibiofouling of poly(carboxybetaine acrylamide) (polyCBAA) brush surfaces.

Single-molecule profiling of per- and polyfluoroalkyl substances by cyclodextrin mediated host-guest interactions within a biological nanopore.

Biological nanopores are increasingly used in molecular sensing due to their single-molecule sensitivity. The detection of per- and polyfluoroalkyl substances (PFAS) like perfluorooctanoic acid and perfluorooctane sulfonic acid is critical due to their environmental prevalence and toxicity. Here, we investigate selective interactions between PFAS and four cyclodextrin (CD) variants (α-, β-, γ-, and 2-hydroxypropyl-γ-CD) within an α-hemolysin nanopore.

Atomistic Simulations of Hydration and Antibiofouling Behavior of Amphiphilic Polymer Brush Surfaces Functionalized with TMAO and Short Fluorocarbon.

Developing fouling-resistant materials is of paramount interest in marine industries and biomedical applications. In this work, we studied the interfacial hydration and surface-protein interactions of the amphiphilic brush surface functionalized with hybrid hydrophilic trimethylamine -oxide (TMAO) and hydrophobic pentafluoroethyl groups using a combination of atomistic molecular dynamics simulations and free-energy computations. Our results show that while the interfacial hydration density of the amphiphilic surface slightly decreases with the introduction of small fluorocarbons compared to that of the pure TMAO-functionalized surface, the amphiphilic surface remains relatively strong in resisting protein adsorption.

Hydrophilic Coating Microstructure Mediates Acute Drug Transfer in Drug-Coated Balloon Therapy.

Drug-coated balloon (DCB) therapy is a promising endovascular treatment for obstructive arterial disease. The goal of DCB therapy is restoration of lumen patency in a stenotic vessel, whereby balloon deployment both mechanically compresses the offending lesion and locally delivers an antiproliferative drug, most commonly paclitaxel (PTX) or derivative compounds, to the arterial wall. Favorable long-term outcomes of DCB therapy thus require predictable and adequate PTX delivery, a process facilitated by coating excipients that promotes rapid drug transfer during the inflation period.

Novel Payloads to Mitigate Maladaptive Inward Arterial Remodeling in Drug-Coated Balloon Therapy.

Drug-coated balloon therapy is a minimally invasive endovascular approach to treat obstructive arterial disease, with increasing utilization in the peripheral circulation due to improved outcomes as compared to alternative interventional modalities. Broader clinical use of drug-coated balloons is limited by an incomplete understanding of device- and patient-specific determinants of treatment efficacy, including late outcomes that are mediated by postinterventional maladaptive inward arterial remodeling. To address this knowledge gap, we propose a predictive mathematical model of pressure-mediated femoral artery remodeling following drug-coated balloon deployment, with account of drug-based modulation of resident vascular cell phenotype and common patient comorbidities, namely, hypertension and endothelial cell dysfunction.

Engineering Biological Nanopore Approaches toward Protein Sequencing.

Biotechnological innovations have vastly improved the capacity to perform large-scale protein studies, while the methods we have for identifying and quantifying individual proteins are still inadequate to perform protein sequencing at the single-molecule level. Nanopore-inspired systems devoted to understanding how single molecules behave have been extensively developed for applications in genome sequencing. These nanopore systems are emerging as prominent tools for protein identification, detection, and analysis, suggesting realistic prospects for novel protein sequencing.

Molecular mechanism of GPCR spatial organization at the plasma membrane.

G-protein-coupled receptors (GPCRs) mediate many critical physiological processes. Their spatial organization in plasma membrane (PM) domains is believed to encode signaling specificity and efficiency. However, the existence of domains and, crucially, the mechanism of formation of such putative domains remain elusive.

Cytomegalovirus and Cardiovascular Disease: A Hypothetical Role for Viral G-Protein-Coupled Receptors in Hypertension.

Cytomegalovirus (CMV) is a member of the β-herpesviruses and is ubiquitous, infecting 50%-99% of the human population depending on ethnic and socioeconomic conditions. CMV establishes lifelong, latent infections in their host. Spontaneous reactivation of CMV is usually asymptomatic, but reactivation events in immunocompromised or immunosuppressed individuals can lead to severe morbidity and mortality.

Microcanonical Thermodynamics of Small Ideal Gas Systems.

We consider the thermal, mechanical, and chemical contact of two subsystems composed of ideal gases, both of which are not in the thermodynamic limit. After contact, the combined system is isolated, and the entropy is determined through the use of its standard connection to the phase space density (PSD), where only those microstates at a given energy value are counted. The various intensive properties of these small systems that follow from a derivative of the PSD, such as the temperature, pressure, and chemical potential (evaluated via a backward difference), while equal when the two subsystems are in equilibrium are nevertheless found not to behave in accordance with what is expected from macroscopic thermodynamics.

Soluble and insoluble protein aggregates, endoplasmic reticulum stress, and vascular dysfunction in Alzheimer's disease and cardiovascular diseases.

Dementia refers to a particular group of symptoms characterized by difficulties with memory, language, problem-solving, and other thinking skills that affect a person's ability to perform everyday activities. Alzheimer's disease (AD) is the most common form of dementia, affecting about 6.2 million Americans aged 65 years and older.

Liquid-Phase Effects on Adsorption Processes in Heterogeneous Catalysis.

Aqueous solvation free energies of adsorption have recently been measured for phenol adsorption on Pt(111). Endergonic solvent effects of ∼1 eV suggest solvents dramatically influence a metal catalyst's activity with significant implications for the catalyst design. However, measurements are indirect and involve adsorption isotherm models, which potentially reduces the reliability of the extracted energy values.

Self-Assembling Toroidal Cell Constructs for Tissue Engineering Applications.

Developing tissues have intricate, three-dimensional (3D) organizations of cells and extracellular matrix (ECM) that provide the framework necessary to meet morphogenic and necessary demands. Migrating cells, in vivo, are exposed to numerous conflicting signals: chemokines, ECM, growth factors, and physical forces. While most of these have been studied individually in vivo or in vitro, our understanding of how cells integrate these various signals is lacking.

On Using the BMCSL Equation of State to Renormalize the Onsager Theory Approach to Modeling Hard Prolate Spheroidal Liquid Crystal Mixtures.

Modifications to the traditional Onsager theory for modeling isotropic-nematic phase transitions in hard prolate spheroidal systems are presented. Pure component systems are used to identify the need to update the Lee-Parsons resummation term. The Lee-Parsons resummation term uses the Carnahan-Starling equation of state to approximate higher-order virial coefficients beyond the second virial coefficient employed in Onsager's original theoretical approach.

The Association Between Curvature and Rupture in a Murine Model of Abdominal Aortic Aneurysm and Dissection.

Background: Mouse models of abdominal aortic aneurysm (AAA) and dissection have proven to be invaluable in the advancement of diagnostics and therapeutics by providing a platform to decipher response variables that are elusive in human populations. One such model involves systemic Angiotensin II (Ang-II) infusion into low density-lipoprotein receptor-deficient (LDLr-/-) mice leading to intramural thrombus formation, inflammation, matrix degradation, dilation, and dissection. Despite its effectiveness, considerable experimental variability has been observed in AAAs taken from our Ang-II infused LDLr-/- mice (n=12) with obvious dissection occurring in 3 samples, outer bulge radii ranging from 0.

How Membrane Geometry Regulates Protein Sorting Independently of Mean Curvature.

Biological membranes have distinct geometries that confer specific functions. However, the molecular mechanisms underlying the phenomenological geometry/function correlations remain elusive. We studied the effect of membrane geometry on the localization of membrane-bound proteins.

Quantifying Mg Binding to ssDNA Oligomers: A Self-Consistent Field Theory Study at Varying Ionic Strengths and Grafting Densities.

The performance of aptamer-based biosensors is crucially impacted by their interactions with physiological metal ions, which can alter their structures and chemical properties. Therefore, elucidating the nature of these interactions carries the utmost importance in the robust design of highly efficient biosensors. We investigated Mg 2 + binding to varying sequences of polymers to capture the effects of ionic strength and grafting density on ion binding and molecular reorganization of the polymer layer.

Obstacles to translating the promise of nanoparticles into viable amyloid disease therapeutics.

Nanoparticles (NPs) constitute a powerful therapeutic platform with exciting prospects as potential inhibitors of amyloid-[Formula: see text] (Aβ) aggregation, a process associated with Alzheimer's disease (AD). Researchers have synthesized and tested a large collection of NPs with disparate sizes, shapes, electrostatic properties and surface ligands that evoke a variety of responses on Aβ aggregation. In spite of a decade of research on the NP-Aβ system and many promising experimental results, NPs have failed to progress to any level of clinical trials for AD.

Determining the Potential of Mean Force for Amyloid-β Dimerization: Combining Self-Consistent Field Theory with Molecular Dynamics Simulation.

Amyloid-β (Aβ) protein aggregates through a complex pathway to progress from monomers to soluble oligomers and ultimately insoluble fibrils. Because of the dynamic nature of aggregation, it has proven exceedingly difficult to determine the precise interactions that lead to the formation of transient oligomers. Here, a statistical thermodynamic model has been developed to elucidate these interactions.

Mechanical and geometrical determinants of wall stress in abdominal aortic aneurysms: A computational study.

An aortic aneurysm (AA) is a focal dilatation of the aortic wall. Occurrence of AA rupture is an all too common event that is associated with high levels of patient morbidity and mortality. The decision to surgically intervene prior to AA rupture is made with recognition of significant procedural risks, and is primarily based on the maximal diameter and/or growth rate of the AA.

Membrane Curvature and Lipid Composition Synergize To Regulate N-Ras Anchor Recruitment.

Proteins anchored to membranes through covalently linked fatty acids and/or isoprenoid groups play crucial roles in all forms of life. Sorting and trafficking of lipidated proteins has traditionally been discussed in the context of partitioning to membrane domains of different lipid composition. We recently showed that membrane shape/curvature can in itself mediate the recruitment of lipidated proteins.

Influence of gold nanoparticle surface chemistry and diameter upon Alzheimer's disease amyloid-β protein aggregation.

Background: Deposits of aggregated amyloid-β protein (Aβ) are a pathological hallmark of Alzheimer's disease (AD). Thus, one therapeutic strategy is to eliminate these deposits by halting Aβ aggregation. While a variety of possible aggregation inhibitors have been explored, only nanoparticles (NPs) exhibit promise at low substoichiometric ratios.

A mechanical argument for the differential performance of coronary artery grafts.

Coronary artery bypass grafting (CABG) acutely disturbs the homeostatic state of the transplanted vessel making retention of graft patency dependent on chronic remodeling processes. The time course and extent to which remodeling restores vessel homeostasis will depend, in part, on the nature and magnitude of the mechanical disturbances induced upon transplantation. In this investigation, biaxial mechanical testing and histology were performed on the porcine left anterior descending artery (LAD) and analogs of common autografts, including the internal thoracic artery (ITA), radial artery (RA), great saphenous vein (GSV) and lateral saphenous vein (LSV).

Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases.

Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for enrichment in raft-like liquid-ordered phases; enrichment was driven by relief of lateral pressure upon anchor insertion and most likely affects the localization of lipidated proteins in general.

Mode specific elastic constants for the gel, liquid-ordered, and liquid-disordered phases of DPPC/DOPC/cholesterol model lipid bilayers.

Using microscopic molecular theory, we determine the bending and saddle-splay constants of three-component lipid bilayers. The membrane contains cholesterol, dipalmitoyl-phosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC) and the predictions of the theory have been shown to qualitatively reproduce phase diagrams of giant unilamellar vesicles (GUVs) of the same three components. The bending and saddle-splay constants were calculated for the gel, liquid-ordered (lo) and liquid-disordered (ld) phases.