Opposing roles of organic salts on mini-protein structure.

We investigated the effects of 1-ethyl-3-methylimidazolium chloride ([EMIM][Cl]) and choline chloride ([Chol][Cl]) on the local environment and conformational landscapes of Trp-cage and Trpzip4 mini-proteins using experimental and computational approaches. Fluorescence experiments and computational simulations revealed distinct behaviors of the mini-proteins in the presence of these organic salts. [EMIM][Cl] showed a strong interaction with Trp-cage, leading to fluorescence quenching and destabilization of its native structural interactions.

Recovery of enzyme structure and activity following rehydration from ionic liquid.

Long-term preservation of proteins at room temperature continues to be a major challenge. Towards using ionic liquids (ILs) to address this challenge, here we present a combination of experiments and simulations to investigate changes in lysozyme upon rehydration from IL mixtures using two imidazolium-based ILs (1-ethyl-3-methylimidazolium ethylsulfate, [EMIM][EtSO] and 1-ethyl-3-methylimidazolium diethylphosphate, [EMIM][EtPO]). Various spectroscopic experiments and molecular dynamics simulations are performed to ascertain the structure and activity of lysozyme.

Dual mechanism of ionic liquid-induced protein unfolding.

Ionic liquids (ILs) are gaining attention as protein stabilizers and refolding additives. However, varying degrees of success with this approach motivates the need to better understand fundamental IL-protein interactions. A combination of experiment and simulation is used to investigate the thermal unfolding of lysozyme in the presence of two imidazolium-based ILs (1-ethyl-3-methylimidazolium ethylsulfate, [EMIM][EtSO4] and 1-ethyl-3-methylimidazolium diethylphosphate, [EMIM][Et2PO4]).

Living Supramolecular Polymerization of DNA.

Recently there have been notable synthetic successes in supramolecular polymerization. By contrast, it has long been known that DNA can undergo supramolecular polymerization (concatemerization). Concatemerization is a step-like polymerization and consequently suffers from broad molecular weight distributions and generally undesirable cyclization reactions.

Micelle co-assembly in surfactant/ionic liquid mixtures.

Hypothesis: The phase behavior of amphiphiles is known to depend on their solvent environment. The organic character of ionic liquids suggested the possibility to tune surfactant aggregation, even in the absence of water, by selection of appropriate ionic liquid chemistry. To that end the behavior of the surfactant sodium dodecylsulfate in a chemically similar imidazolium ionic liquid, 1-ethyl-3-methyl imidazolium ethylsulfate, was explored.

Lysozyme Solubility and Conformation in Neat Ionic Liquids and Their Mixtures with Water.

The room temperature solubility of a number of model proteins is assessed for a diverse set of neat ionic liquids (ILs). For two soluble protein-IL pairs, lysozyme in [C2MIM][EtSO4] (1-ethyl-3-methylimidazolium ethylsulfate) and in [C2,4,4,4P][Et2PO4] (tributyl(ethyl)phosphonium diethylphosphate), protein solubility and structure at various temperatures are probed by dynamic light scattering (assessing dissolved molecular size), turbidimetry (reflecting degree of solubility), and Fourier transform infrared spectroscopy (uncovering helical secondary structure). As compared to aqueous environments, [C2,4,4,4P][Et2PO4] thermally stabilizes protein size and secondary structure while [C2MIM][EtSO4] does the opposite.

Interplay of Dynamical Properties between Ionic Liquids and Ionic Surfactants: Mechanism and Aggregation.

The dynamical and aggregation behaviors of sodium dodecyl sulfate (SDS) in 1-ethyl-3-methylimidazolium ethylsulfate [EMIM+][EtSO4–] are characterized experimentally and computationally. A retardation of the ionic liquid (IL) and SDS diffusion coefficients with a concentration increase of SDS is observed. In agreement with experiments, aggregation is detected for concentrations higher than the experimental critical micelle concentration (CMC), which is mostly driven by alkyl tail aggregation.

Effects of prolonged ethanol lock exposure to carbothane- and silicone-based hemodialysis catheters: a 26-week study.

Purpose: Antibiotic locks in catheter-dependent chronic hemodialysis patients reduce the rate of catheter-related bloodstream infections (CRBSIs), but may be associated with the development of resistant bacteria. Ethanol-based catheter locks may provide a better alternative; however, there are limited data on the long-term integrity of dialysis catheters exposed to ethanol.

Methods: We performed in vitro testing of two types of hemodialysis catheters—silicone (SLC) and carbothane (CBT) based—with a 70% ethanol lock (EL) versus heparin lock (HL) for 26 weeks.

DNA nanostructures: a shift from assembly to applications.

The specificity of DNA hybridization allows for the modular design of 2D and 3D shapes with wide-ranging applications including sensors, actuators, and even logic devices. The inherent biocompatibility of DNA and the ability to produce monodisperse structures of controlled shape and size make DNA nanostructures of interest as potential drug and gene delivery vehicles. In this review, we discuss several new approaches for the assembly of DNA nanostructures, advances in the modeling of these structures, and we highlight recent studies on the use of DNA nanotechnology for therapeutic applications such as drug delivery in tumor models.

Aptamer-targeted DNA nanostructures for therapeutic delivery.

DNA-based nanostructures have been widely used in various applications due to their structural diversity, programmability, and uniform structures. Their intrinsic biocompatibility and biodegradability further motivates the investigation of DNA-based nanostructures as delivery vehicles. Incorporating AS1411 aptamers into DNA pyramids leads to enhanced intracellular uptake and selectively inhibits the growth of cancer cells, achieved without the use of transfection reagents.

Cell adhesion mechanisms on laterally mobile polymer films.

In contrast with the majority of substrates used to study cell adhesion, the natural extracellular matrix (ECM) is dynamic and remodeled over time. Here we use amphiphilic block copolymers to create self-assembled supported films with tunable lateral mobility. These films are intended to serve as partial mimics of the ECM in order to better understand cell adhesion responses, specifically in the context of dynamic substrates.

Charge screening between anionic and cationic surfactants in ionic liquids.

The aggregation and interfacial behavior of mixtures of anionic (sodium dodecylsulfate, SDS) and cationic (dodecylammonium bromide, DTAB) surfactants were investigated. A room-temperature ionic liquid (IL) was explored as a solvent for the SDS/DTAB system and compared to water. The critical micelle concentration (cmc) and composition in mixed micelles were determined for both solvents.

Effects of short elastin-like peptides on filamentous particles and their transition behavior.

While elastin-like polypeptides and peptides (ELPs) have been used for various stimulus-responsive applications, details of their switching remain unclear. We therefore constructed a novel series of filamentous phage particles displaying a high surface density of short ELPs. The surface display of ELPs did not disrupt either particle shape or dimensions, and the resulting ELP-phage particles were colloidally stable over several weeks.

Critical solution behavior of poly(N-isopropyl acrylamide) in ionic liquid-water mixtures.

The wide diversity of room-temperature ionic liquids (ILs) presents opportunities for studying, and controlling, polymer phase behavior. We have examined the phase behavior of poly(N-isopropyl acrylamide) (PNIPAM) in imidazolium ILs and their mixtures with water. We find there is a strong influence of the IL anion; specifically, the tetrafluoroborate anion yields a complex phase diagram with both LCST and UCST-type regimes.

DNA-based delivery vehicles: pH-controlled disassembly and cargo release.

Non-Watson-Crick base pairing provides an in situ approach for actuation of DNA nanostructures through responses to solution conditions. Here we demonstrate this concept by using physiologically-relevant changes in pH to regulate DNA pyramid assembly/disassembly and to control the release of protein cargo.

Phage-based molecular probes that discriminate force-induced structural states of fibronectin in vivo.

Applied forces and the biophysical nature of the cellular microenvironment play a central role in determining cellular behavior. Specifically, forces due to cell contraction are transmitted into structural ECM proteins and these forces are presumed to activate integrin "switches." The mechanism of such switches is thought to be the partial unfolding of integrin-binding domains within fibronectin (Fn).

The role of defects on the assembly and stability of DNA nanostructures.

Defects are known to underlie the mechanical properties of materials, especially so at the nanoscale. Using four compositionally identical DNA triangles, defect density is found to be inversely correlated with assembly efficiency and melting temperature. These findings are supported by a series of experiments with more complex DNA pyramids.

Solubility and aggregation of charged surfactants in ionic liquids.

Room-temperature ionic liquids (ILs) exhibit a unique set of properties, leading to opportunities for numerous applications. To obtain a better understanding of IL interfaces at a molecular level, we combined charged surfactants with ILs and studied their interfacial behavior. The critical micelle concentration (cmc) of each surfactant-IL pair was determined from both solubility phase diagrams and isotherms.

Design, assembly, and activity of antisense DNA nanostructures.

Discrete DNA nanostructures allow simultaneous features not possible with traditional DNA forms: encapsulation of cargo, display of multiple ligands, and resistance to enzymatic digestion. These properties suggested using DNA nanostructures as a delivery platform. Here, DNA pyramids displaying antisense motifs are shown to be able to specifically degrade mRNA and inhibit protein expression in vitro, and they show improved cell uptake and gene silencing when compared to linear DNA.

Thermodynamics of monolayers formed by mixtures of phosphatidylcholine/phosphatidylserine.

In this work we obtain the thermodynamic properties of mixed (1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine) PC and (1-stearoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (sodium salt)) PS monolayers. Measurements of compressibility (isotherms, bulk modulus, and excess area per molecule) and surface potential show that the properties of monolayers at the air-water interface depend on the concentration of ions (Na(+) and K(+)) and the proportion of PS in the mixture. The dependence on PS arises because the molecule is originally bound to a Na(+) counterion; by increasing the concentration of ions the entropy changes, creating a favorable system for the bound counterions of PS to join the bulk, leaving a negatively charged molecule.

Controlling forces and pathways in self-assembly using viruses and DNA.

The ability of both viruses and DNA to self-assemble in solution has continues to enable numerous applications at the nanoscale. Here we review the relevant interactions dictating the assembly of these structures, as well as discussing how they can be exploited experimentally. Because self-assembly is a process, we discuss various strategies for achieving spatial and temporal control.

Surfactant-mediated ion exchange and charge reversal at ionic liquid interfaces.

Room-temperature ionic liquids (ILs) exhibit a unique set of properties due to their charged character, presenting opportunities for numerous applications. Here, we show that the combination of charged surfactants with ILs leads to rich interfacial behavior due to the interplay between electrostatic and surface forces. Using traditional measures of surface activity and X-ray photoelectron spectroscopy (XPS), we find that sodium alkyl sulfates and alkyl trimethylammonium bromides are, indeed, surface-active at the air-IL interfaces of both [EMIM][EtSO(4)] and [BHEDMA][MeSO(3)].

Controlled interfacial assembly and transfer of brushlike copolymer films.

The self-assembly and compression of polybutadiene-bpoly(ethylene oxide) (PBd-PEO) at the air/water interface enables control over surface density, height, and film structure. Interfacial transfer was performed by a combination of Langmuir-Blodgett (LB) and Langmuir-Schaefer (LS) techniques, resulting in monolayer and bilayer films. Ellipsometry and wettability results were used to characterize the efficiency of transfer and to determine the properties of the resulting films, confirming a brushlike monolayer.

Enhanced resistance of DNA nanostructures to enzymatic digestion.

The ability of nucleases to perform their catalytic functions depends on the sequence and structural features of target DNA substrates. Due to their size and shape, several DNA tetrahedra are resistant to the action of specific and non-specific nucleases. Such enhanced stability is a key requirement for DNA nanostructures to be useful as delivery vehicles.

Incorporating stimulus-responsive character into filamentous virus assemblies.

Controlling interactions between building blocks, in either guided- or self-assemblies, is becoming increasingly important for the creation of functional materials. We have focused our attention on the well-known model assembly, the filamentous bacteriophage, where our strategy is to selectively alter surface features by focusing on spatially distinct capsid proteins. Towards introducing stimulus-responsive behavior in these flexible, rod-like particles, we have introduced elastin-like polypeptide (ELP) motifs of isoleucine and tyrosine "guest" residues by recombinant DNA methods.