Modeling polymer grafted nanoparticle networks reinforced by high-strength chains.

Using a multi-scale computational approach, we determine the effect of introducing a small fraction of high-strength connections between cross-linked nanoparticles. The nanoparticles' rigid cores are decorated with a corona of grafted polymers, which contain reactive functional groups at the chain ends. With the overlap of neighboring coronas, these reactive groups can form weak labile bonds, which can reform after breakage, or stronger bonds, which rupture irreversibly and thus, the nanoparticles are interconnected by dual cross-links.

Fluid-driven motion of passive cilia enables the layer to expel sticky particles.

Inspired by marine organisms that utilize active cilia to prevent the biofouling of their surfaces, we use computational and theoretical modeling to determine if passive cilia, which are driven to undulate by an oscillatory shear flow, can be harnessed for antifouling applications. By modeling the oscillating shear flow near a ciliated wall within a channel, we show that the fluid-driven motion of cilia enables the layer to repel adhesive particles away from the surface. Compared to the behavior of the system in a non-oscillating shear, the oscillations also help transport the particles more rapidly along the flow direction.

Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission.

The vast majority of new HIV infections result from relatively inefficient transmission of the virus across mucosal surfaces during sexual intercourse. A consequence of this inefficiency is that small numbers of transmitted founder viruses initiate most heterosexual infections. This natural bottleneck to transmission has stimulated efforts to develop interventions that are aimed at blocking this step of the infection process.

Modeling chemoresponsive polymer gels.

Stimuli-responsive gels are vital components in the next generation of smart devices, which can sense and dynamically respond to changes in the local environment and thereby exhibit more autonomous functionality. We describe recently developed computational methods for simulating the properties of such stimuli-responsive gels in the presence of optical, chemical, and thermal gradients. Using these models, we determine how to harness light to drive shape changes and directed motion in spirobenzopyran-containing gels.

Synthesis and structure-activity relationships of novel ecdysteroid dioxolanes as MDR modulators in cancer.

Ecdysteroids, molting hormones of insects, can exert several mild, non-hormonal bioactivities in mammals, including humans. In a previous study, we have found a significant effect of certain derivatives on the ABCB1 transporter mediated multi-drug resistance of a transfected murine leukemia cell line. In this paper, we present a structure-activity relationship study focused on the apolar dioxolane derivatives of 20-hydroxyecdysone.

Self-healing vesicles deposit lipid-coated Janus particles into nanoscopic trenches.

Using dissipative particle dynamics (DPD) simulations, we model the interaction between nanoscopic lipid vesicles and Janus nanoparticles localized on an adhesive substrate in the presence of an imposed flow. The system is immersed in a hydrophilic solution, and the hydrophilic substrate contains nanoscopic trenches, which are either step- or wedge-shaped. The fluid-driven vesicle successfully picks up Janus particles on the substrate, transports these particles as cargo along the surface, and then drops off the particles into the trenches.

Harnessing interfacially-active nanorods to regenerate severed polymer gels.

With newly developed computational approaches, we design a nanocomposite that enables self-regeneration of the gel matrix when a significant portion of the material is severed. The cut instigates the dynamic cascade of cooperative events leading to the regrowth. Specifically, functionalized nanorods localize at the new interface and initiate atom transfer radical polymerization with monomers and cross-linkers in the outer solution.

1H and 13C NMR investigation of 20-hydroxyecdysone dioxolane derivatives, a novel group of MDR modulator agents.

The synthesis, structure elucidation and the complete (1)H and (13)C signal assignment of a series of dioxolane derivatives of 20-hydroxyecdysone, synthesized as novel modulators of multidrug resistance, are presented. The structures and NMR signal assignment were established by comprehensive one-dimensional and two-dimensional NMR spectroscopy supported by mass spectrometry.

Active ciliated surfaces expel model swimmers.

Continually moving cilia on the surface of marine organisms provide a natural defense against biofouling. To probe the physical mechanisms underlying this antifouling behavior, we integrate the lattice Boltzmann and immersed boundary methods and undertake the first computational studies of the interactions between actuated, biomimetic cilia and a model swimmer. We find that swimmers are effectively "knocked away" from the ciliated surface through a combination of steric repulsion and locally fluctuating flows.

"Zero-dimensional" single-walled carbon nanotubes.

The shorter, the more dispersible: An iterative, emulsion-based shortening technique has been used to reduce the length of single-walled carbon nanotubes (SWNTs) to the same order of magnitude as their diameter (ca. 1 nm), thus achieving an effectively "zero-dimensional" structure with improved dispersibility and, after hydroxylation, long-term water solubility. Finally, zero-dimensional SWNTs were positively identified using mass spectrometry for the first time.

Quantitative liver lesion volume determination by nanoparticle-based SPECT.

Purpose: The aim of this paper is to present a simple and quantitative data analysis method with a new potential in the application of liver single-photon emission computed tomography (SPECT) imaging. We have established quantitative SPECT/computed tomography (CT) in vivo imaging protocols for determination of liver tumor burden based on the known role of Kupffer cells in cancer of the liver.

Procedures: As it is also known that functional Kupffer cells accumulate particulate material contained in the arterial blood of liver supply, we used radiolabeled macro-aggregated albumin particles ([(99m)Tc]-MAA) injected intravenously to image liver disease.

Nano-pipette directed transport of nanotube transmembrane channels and hybrid vesicles.

Using computational modeling, we simulate the interactions between a nanopipette and transmembrane, end-functionalized nanotubes that are localized within flat bilayers or nanoscopic vesicles. The functional groups (hairs) provide a "handle" for the moving pipette to controllably pick up and move the nanotubes to specific locations in the flat membrane, or the hybrid vesicle to specified regions on a surface. The ability to localize these hybrid vesicles on surfaces paves the way for creating nanoreactor arrays in fluidic devices.

Using light to guide the motion of nanorods in photoresponsive binary blends: designing hierarchically structured nanocomposites.

One of the challenges in creating high-performance polymer nanocomposites is establishing effective routes for tailoring the morphology of both the polymer mixture and the dispersed nanoparticles, which contribute desirable optical, electrical, and mechanical properties. Using computational modeling, we devise an effective method for simultaneously controlling the spatial regularity of the polymer phases and the distribution of the rods within this matrix. We focus on mixtures of photosensitive AB binary blends and A-coated nanorods; in the presence of light, the binary blends undergo a reversible chemical reaction and phase separation to yield a morphology resembling that of microphase-separated diblock copolymers.

Experience with stent implantation in malignant esophageal strictures: analysis of 1185 consecutive cases.

Purpose: The aim of this retrospective study was to analyze the experience in endoprosthesis implantation in cases of malignant esophageal strictures.

Methods: A total of 1185 consecutive patients underwent endoprosthesis implantation: through open surgery in 42 cases and by endoscopy in 1143 cases.

Results: Stent implantation was performed successfully in 61.

Broad protection against influenza infection by vectored immunoprophylaxis in mice.

Neutralizing antibodies that target epitopes conserved among many strains of influenza virus have been recently isolated from humans. Here we demonstrate that adeno-associated viruses (AAV) encoding two such broadly neutralizing antibodies are protective against diverse influenza strains. Serum from mice that received a single intramuscular AAV injection efficiently neutralized all H1, H2 and H5 influenza strains tested.

Size selectivity in artificial cilia-particle interactions: mimicking the behavior of suspension feeders.

Inspired by the ability of marine suspension feeders to selectively capture small particles by their hairlike cilia, we simulate the interaction between artificial cilia and microscopic particles of different sizes to determine if a purely synthetic system can display analogous size-selective behavior. Our computational approach specifically models the capture of particles suspended in the surrounding fluid by adhesive filaments, which are anchored by one end to a surface. Via this model, we show that this size selectivity can arise as a result of adhesive and hydrodynamic interactions in the system.

Chemo-responsive, self-oscillating gels that undergo biomimetic communication.

Species ranging from single-cell organisms to social insects can undergo auto-chemotaxis, where the entities move towards a chemo-attractant that they themselves emit. Polymer gels undergoing the self-oscillating Belousov-Zhabotinsky (BZ) reaction exhibit autonomous, periodic pulsations, which produce chemical species collectively referred to as the activator. The diffusion of this activator into the surrounding solution affects the dynamic behavior of neighboring BZ gels and hence, the BZ gels not only emit, but also respond to self-generated chemical gradients.

Harnessing fluid-driven vesicles to pick up and drop off Janus particles.

Using dissipative particle dynamics (DPD) simulations, we model the interaction between nanoscopic lipid vesicles and Janus nanoparticles in the presence of an imposed flow. Both the vesicle and Janus nanoparticles are localized on a hydrophilic substrate and immersed in a hydrophilic solution. The fluid-driven vesicle successfully picks up Janus particles on the substrate and transports these particles as cargo along the surface.

Reconfigurable assemblies of active, autochemotactic gels.

Using computational modeling, we show that self-oscillating Belousov-Zhabotinsky (BZ) gels can both emit and sense a chemical signal and thus drive neighboring gel pieces to spontaneously self-aggregate, so that the system exhibits autochemotaxis. To the best of our knowledge, this is the closest system to the ultimate self-recombining material, which can be divided into separated parts and the parts move autonomously to assemble into a structure resembling the original, uncut sample. We also show that the gels' coordinated motion can be controlled by light, allowing us to achieve selective self-aggregation and control over the shape of the gel aggregates.

Coassembly of nanorods and photosensitive binary blends: "combing" with light to create periodically ordered nanocomposites.

Using computational modeling, we establish a means of controlling structure formation in nanocomposites that encompass nanorods and a photosensitive binary blend. The complex cooperative interactions in the system include a preferential wetting interaction between the rods and one of the phases in the blend, steric repulsion between the coated rods, and the response of the binary blend to light. Under uniform illumination, the binary mixture undergoes both phase separation and a reversible chemical reaction, leading to a morphology resembling that of a microphase-separated diblock copolymer.

Antibody gene transfer for HIV immunoprophylaxis.

Antibody gene transfer, which involves the delivery of genes that encode potent, broadly neutralizing antibodies to human immunodeficiency virus (HIV), is a promising new strategy for preventing HIV infection. A satellite symposium at the AIDS Vaccine 2012 conference brought together many of the groups working in this field.

Fibers with integrated mechanochemical switches: minimalistic design principles derived from fibronectin.

Inspired by molecular mechanisms that cells exploit to sense mechanical forces and convert them into biochemical signals, chemists dream of designing mechanochemical switches integrated into materials. Using the adhesion protein fibronectin, whose multiple repeats essentially display distinct molecular recognition motifs, we derived a computational model to explain how minimalistic designs of repeats translate into the mechanical characteristics of their fibrillar assemblies. The hierarchy of repeat-unfolding within fibrils is controlled not only by their relative mechanical stabilities, as found for single molecules, but also by the strength of cryptic interactions between adjacent molecules that become activated by stretching.

Complex formation of EphB1/Nck/Caskin1 leads to tyrosine phosphorylation and structural changes of the Caskin1 SH3 domain.

Background: Scaffold proteins have an important role in the regulation of signal propagation. These proteins do not possess any enzymatic activity but can contribute to the formation of multiprotein complexes. Although scaffold proteins are present in all cell types, the nervous system contains them in the largest amount.