Biomedical subjects

Frank S Bates

Publications and source records attributed to Frank S Bates.

11 recordsLinked to original sources

PubMed2006

Disordered network state in hydrated block-copolymer surfactants.

Hydration of poly(butadiene-b-ethylene oxide) diblock copolymers leads to various ordered and disordered phases, analogous to the aqueous phase behavior of surfactants and lipids. Small-angle x-ray scattering measurements corroborated by cryogenic scanning electron microscopy imaging reveal a random network (N) morphology at polymer compositions and water content intermediate to those associated with ordered cylinders (H1) and lamellae (L). This sequence of self-assembled structures is strikingly similar to the phase behavior of certain water-oil-surfactant microemulsions.

Butadienes↗

PubMed2006

Influence of conformational asymmetry on the phase behavior of ternary homopolymer/block copolymer blends around the bicontinuous microemulsion channel.

We have developed a new ternary polymeric system, poly(ethylene-alt-propylene) (PEP)/poly(butylene oxide) (PBO)/PEP-PBO, to study the complex phase behavior near the bicontinuous microemulsion phase channel. The molecular weights of the PEP and PBO homopolymers are 2600 and 3050 g/mol, respectively, and the copolymer is 23.4 kg/mol with volume fraction composition fPBO=0.49. A combination of small-angle neutron scattering, small-angle X-ray scattering, rheology, optical microscopy, and visual oil bath measurements was employed to map out the phase diagrams at five fixed homopolymer PBO/PEP ratios, ranging from 40/60 to 60/40 by volume, with copolymer concentrations ranging from 0 to 100%. It was found that the bicontinuous microemulsion channel is consistently cut off at low temperature by a hexagonal phase. We attribute this phenomenon to the effect of the conformational asymmetry between the PEP and PBO species, whereby the more flexible PBO component induces a spontaneous curvature toward the PBO domains. These findings complement previous descriptions of the isopleth phase diagrams for A/B/A-B systems and identify a new design variable for preparing bicontinuous phases.

Journal Article↗

PubMed2006

Mesoporous membrane templated by a polymeric bicontinuous microemulsion.

We demonstrate a facile method for preparing a novel nanoporous material with an isotropic, three-dimensionally continuous pore structure from a polymeric bicontinuous microemulsion precursor, which consists of two immiscible homopolymers and the corresponding diblock copolymer. The protocol for the generation of nanopores is selective cross-linking of one domain with the subsequent removal of the other domain by solvent dissolution.

Crystallization↗

PubMed2005

Adhesion of polymer vesicles.

The adhesion and bending modulus of polybutadiene-poly(ethylene oxide) block copolymer vesicles made from a bidisperse mixture of polymers is measured using micropipette aspiration. The adhesion energy between biotinylated vesicles and avidin beads is modeled by incorporating the extension of the adhesive ligands above the surface brush of the vesicle according to the blob model of bidisperse polymer mixtures of Komura and Safran assuming the polymer brush at the surface of the vesicle is compact. The same model accurately reproduces the scaling of the bending modulus with polymer composition.

Avidin↗

PubMed2005

Near-infrared-emissive polymersomes: self-assembled soft matter for in vivo optical imaging.

We demonstrate that synthetic soft materials can extend the utility of natural vesicles, from predominantly hydrophilic reservoirs to functional colloidal carriers that facilitate the biomedical application of large aqueous-insoluble compounds. Near-infrared (NIR)-emissive polymersomes (50-nm- to 50-microm-diameter polymer vesicles) were generated through cooperative self assembly of amphiphilic diblock copolymers and conjugated multi(porphyrin)-based NIR fluorophores (NIRFs). When compared with natural vesicles comprised of phospholipids, polymersomes were uniquely capable of incorporating and uniformly distributing numerous large hydrophobic NIRFs exclusively in their lamellar membranes. Within these sequestered compartments, long polymer chains regulate the mean fluorophore-fluorophore interspatial separation as well as the fluorophore-localized electronic environment. Porphyrin-based NIRFs manifest photophysical properties within the polymersomal matrix akin to those established for these high-emission dipole strength fluorophores in organic solvents, thereby yielding uniquely emissive vesicles. Furthermore, the total fluorescence emanating from the assemblies gives rise to a localized optical signal of sufficient intensity to penetrate through the dense tumor tissue of a live animal. Robust NIR-emissive polymersomes thus define a soft matter platform with exceptional potential to facilitate deep-tissue fluorescence-based imaging for in vivo diagnostic and drug-delivery applications.

Animals↗

PubMed2004

Shear-induced network-to-network transition in a block copolymer melt.

A tricontinuous (10,3)c network phase is documented in a poly(cyclohexylethylene-b-ethylethylene-b-ethylene) triblock copolymer melt based on small-angle x-ray scattering. Application of shear transforms the self-assembled soft material into a single crystal (10,3)d network while preserving the short-range threefold connector geometry. Long-range topological restructuring reduces the space group symmetry, from Fddd to Pnna, maintaining orthorhombic lattice symmetry. Both phases are stable to long time annealing, indicative of nearly degenerate free energies and prohibitive kinetic barriers.

Biophysics↗

PubMed2004

The effect of polymer chain length and surface density on the adhesiveness of functionalized polymersomes.

Giant cell-like polymer vesicles, polymersomes, made from the diblock copolymer poly(ethylene oxide)-polybutadiene (PEO-PBD), have bilayer structures similar to the cell membrane but have superior and tunable properties for storage and stability. We have modified the terminal hydroxyl of the hydrophilic block with biotin-lysine (biocytin), a biologically derived group that imparts specific adhesiveness to a polymer colloid coated with avidin. The functionalized polymer will form vesicles, either on its own or when mixed with unmodified block copolymers that also form vesicles. The incorporation and mixing of the functionalized polymer into vesicle bilayers is measured using a fluorescent version ofbiocytin with confocal microscopy. The fluorescence signal associated with the vesicle is in proportion with the concentration of functional polymer added during vesicle construction. The adhesiveness of polymer vesicles containing functionalized biotinylated polymer to avidin coated microspheres is measured with micropipet aspiration. Two types of polymer vesicles were constructed: one where the functionalized polymer (molecular weight (MW), 10400 Da) was longer than the surrounding unfunctionalized polymer (MW, 3600 Da) and one where the functionalized polymer (MW, 10400 Da) was the same length as the unfunctionalized polymer. In all cases, the avidin-biotin bonds form kinetically trapped crossbridges that impart little tension as they form but require significantly more tension to break. The relative length of the functionalized polymer on the surface of the vesicle is an important determinant for the adhesion of a polymer vesicle but not for the adsorption of soluble avidin. Greater adhesion strengths are seen where the functionalized polymer is longer than the surrounding polymer. The concentration of functionalized polymer at which adhesion is maximal depends on the relative lengths of the polymers. When the functionalized polymer is the same length as the surface brush of the polymersome membrane, the critical tension is maximal at 10 mol % functionalized polymer concentration. However, when the biocytin groups are attached to a polymer which is larger than the surface brush, the critical tension is maximal at 55 mol % functionalized polymer. These results indicate that polymer mixing and length can control the interfacial adhesion of polymer brushes and must be understood to tune polymersome adhesiveness.

Adhesiveness↗

PubMed2003

Polymer vesicles in vivo: correlations with PEG molecular weight.

PEG-modified lipid vesicles have already shown considerable utility in delaying vesicle clearance from the circulation. They are, however, limited in their ability to stably integrate high molar ratios of PEG-lipid due to the high curvature and micellar preference of the very large hydrophilic PEG chain. Polymersomes, by contrast, are vesicles composed entirely of PEG-based block copolymer amphiphiles that are not only more proportionately designed, but also have already been shown to considerably broaden the range of vesicle properties (e.g. stability). Here, polymersomes composed of varying length copolymer chains were injected into rats and found to have in vivo circulation times, tau(1/2), up to about two-fold longer than PEGylated, or Stealth, liposomes. The dependence of tau(1/2) on PEG molecular weight is nonetheless limited by uptake into the liver and spleen-as with liposomes. In vitro incubations of polymersomes in plasma indicate gradual opsonization through plasma protein adsorption, such that, when vesicles are held in an optical trap and presented to a phagocyte, rapid engulfment occurs only after incubation times of similar magnitude to tau(1/2). The stealthiness introduced to liposomes through PEGylation is thus extended here with completely synthetic polymersomes.

Animals↗

PubMed2003

On the origins of morphological complexity in block copolymer surfactants.

Amphiphilic compounds such as lipids and surfactants are fundamental building blocks of soft matter. We describe experiments with poly(1,2-butadiene-b-ethylene oxide) (PB-PEO) diblock copolymers, which form Y-junctions and three-dimensional networks in water at weight fractions of PEOintermediate to those associated with vesicle and wormlike micelle morphologies. Fragmentation of the network produces a nonergodic array of complex reticulated particles that have been imaged by cryogenic transmission electron microscopy. Data obtained with two sets of PB-PEOcompounds indicate that this type of self-assembly appears above a critical molecular weight. These block copolymers represent versatile amphiphiles, mimicking certain low molecular weight three-component (surfactant/water/oil) microemulsions, without addition of a separate hydrophobe.

Butadienes↗

PubMed2002

Time-resolved small-angle x-ray scattering measurements of a polymer bicontinuous microemulsion structure factor under shear.

In situ synchrotron x-ray scattering is used in conjunction with a novel annular cone and plate shear cell to study the nonequilibrium structure factor of a polymer bicontinuous microemulsion within the flow-gradient plane. At equilibrium the scattering is well described by the Teubner-Strey structure factor. In steady shear, the structure factor becomes highly anisotropic, owing to loss of scattering intensity along the flow direction and growth of intensity in peaks that progressively rotate towards the velocity-gradient direction. These results contrast with the predictions of a time-dependent Landau-Ginzburg model of Pätzold and Dawson, which generally predicts suppression of scattered intensity. The model assumption of a uniform velocity profile at the microemulsion length scale may be inappropriate owing to high viscosity contrast between the constituents of this sample. While the model anticipates a "stress-x-ray" rule, the data do not support its existence in this system. Nevertheless, strong connections do exist between x-ray anisotropy and stress during transient flow inception experiments. These connections break down upon flow cessation, where stress decays much more rapidly than anisotropy in the structure factor. The mechanical response of this sample exhibits a Rouse-like spectrum of relaxation times, whereas the second moment tensor used to characterize anisotropy in the structure factor exhibits nearly single-exponential relaxation. A phenomenological upper-convected-Maxwell/Lodge model for the second moment tensor provides essentially quantitative predictions of the structural response in step strain and oscillatory shear flow at moderate strains, although additional nonlinearity is found at higher strains.

Journal Article↗

PubMedDate not supplied

Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling.

Dendritic cells (DCs) play a pivotal role in both immune tolerance and the initiation of immunological responses. The ability to track DCs in vivo is imperative for the development of DC-based cellular therapies and to advance our understanding of DC function and pathophysiology. Here, we conjugate a cell permeable peptide, Tat, to near-infrared (NIR) emissive polymersomes in order to enable efficient intracellular delivery for future DC tracking with these optical probes. NIR imaging allows quantitative, repetitive, in vivo detection of fluorophore-laden cells, at centimeter tissue depths without disturbing cellular function. Flow cytometry and confocal microscopy results indicate that Tat-mediated polymersome delivery to DCs is concentration and time dependent, resulting in punctate intracellular localization. Further, loading cells with Tat NIR emissive polymersomes does not interfere with cytokine-induced DC maturation and has modest effects on DC viability, but has a significant effect on mature DC-induced activation of naive T cells. We observe significant uptake of NIR emissive polymersomes when conjugated to the peptide, with a lower detection limit of 5000 labeled DCs. The extent of polymersome delivery is estimated as 70 000 +/- 10 000 vesicles/cell, equivalent to 0.7 +/- 0.1 fmol of NIR fluorophore. Our studies will enable future in vivo tracking of ex vivo labeled DCs by NIR fluorescence based imaging.

Cell Survival↗