Although shape-memory metal alloys have wide use in medicine
and other areas, improved properties, particularly easy shaping, high
shape stability, and adjustable transition temperature, are realizable
only by polymer systems. In this paper, a polymer system of
shape-memory polymer networks based on oligo(ɛ-caprolactone)
dimethacrylate as crosslinker and n-butyl acrylate as
comonomer was introduced. The influence of two structural parameters,
the molecular weight of oligo(ɛ-caprolactone) dimethacrylate and the
weight content of n-butyl acrylate, on macroscopic
properties of polymer networks such as thermal and mechanical
properties has been investigated. Tensile tests above and below melting
temperature showed a decrease in the elastic modulus with increasing
comonomer weight content. The crystallization behavior of the new
materials has been investigated, and key parameters for the programming
procedure of the temporary shape have been evaluated. Shape-memory
properties have been quantified by thermocyclic experiments. All
samples reached uniform deformation properties with recovery rates
above 99% after 3 cycles. Whereas strain recovery increased with
increasing n-butyl acrylate content, strain fixity
Protein expression after delivery of plasmid DNA to the cell
nucleus depends on the processes of transcription and translation.
Cytotoxic gene-delivery systems may compromise these processes and
limit protein expression. This situation is perhaps most prevalent in
current nonviral polycationic gene-delivery systems in which the
polycationic nature of the delivery system can lead to cytotoxicity. To
approach the problem of creating nontoxic but effective gene-delivery
systems, we hypothesized that by optimizing the balance between polymer
cationic density with endosomal escape moieties, effective gene
transfer with low cytotoxicity could be created. As a model system, we
synthesized a series of polymers whose side-chain termini varied with
respect to the balance of cationic centers and endosomal escape
moieties. Specifically, by polymer-analogous amidation we conjugated
imidazole groups to the ɛ-amines of polylysine in varying mole ratios
(73.5 mol % imidazole, 82.5 mol % imidazole, and 86.5 mol %
imidazole). The primary ɛ-amine terminus of polylysine served as a
model for the cationic centers, whereas the imidazole groups served as
a model for the endosomal escape moieties. These polymers condensed
plasmid DNA into nanostructures <150 nm and possessed little
cytotoxicity in vitro. Transfection efficiency...
Porous polymeric media (polymer foams) are utilized in a wide range of applications, such as thermal and mechanical insulators, solid supports for catalysis, and medical devices. A process for the production of polymer foams has been developed. This process, which is applicable to a wide range of polymers, uses a hydrocarbon particulate phase as a template for the precipitation of the polymer phase and subsequent pore formation. The use of a hydrocarbon template allows for enhanced control over pore structure, porosity, and other structural and bulk characteristics of the polymer foam. Polymer foams with densities as low as 120 mg/cc, porosity as high as 87%, and high surface areas (20 m2/g) have been produced. Foams of poly(l-lactic acid), a biodegradable polymer, produced by this process have been used to engineer a variety of different structures, including tissues with complex geometries such as in the likeness of a human nose.
The fluorescence of a polyanionic conjugated polymer can be quenched by extremely low concentrations of cationic electron acceptors in aqueous solutions. We report a greater than million-fold amplification of the sensitivity to fluorescence quenching compared with corresponding “molecular excited states.” Using a combination of steady-state and ultrafast spectroscopy, we have established that the dramatic quenching results from weak complex formation [polymer(−)/quencher(+)], followed by ultrafast electron transfer from excitations on the entire polymer chain to the quencher, with a time constant of 650 fs. Because of the weak complex formation, the quenching can be selectively reversed by using a quencher-recognition diad. We have constructed such a diad and demonstrate that the fluorescence is fully recovered on binding between the recognition site and a specific analyte protein. In both solutions and thin films, this reversible fluorescence quenching provides the basis for a new class of highly sensitive biological and chemical sensors.
The dependence of the rate on polymer mass was examined for the reaction of four sulfhydryl-directed poly(ethylene glycol) reagents with cysteine residues located in the lumen of the staphylococcal α-hemolysin pore. The logarithms of the apparent rate constants for a particular site in the lumen were proportional to N, the number of repeat units in a polymer chain. The proportionality constant was −(a/D)5/3, where a is the persistence length of the polymer (≈3.5Å) and D is the diameter of the pore. Despite some incongruencies with the assumptions of the derivation, the result suggests that the polymers partition into the lumen of the pore according to the simple scaling law of Daoud and de Gennes, cpore/csolution = exp(−N(a/D)5/3). Therefore, the measured reaction rates yield an estimate of the diameter of the pore and might be applied to determine the approximate dimensions of cavities within other similar proteins.
Sensor formats have been developed for detecting the activity of proteolytic enzymes based on fluorescent conjugated polymer superquenching. These sensors employ a reactive peptide sequence within a tether linking a quencher to a biotin. The peptide binds to sensors containing colocated biotin-binding protein and fluorescent polymer by means of biotin–biotin binding protein interactions, resulting in a strong quenching of polymer fluorescence. Enzyme-mediated cleavage of the peptide results in a reversal of the fluorescence quenching. These assays for protease activity are simple, sensitive, fast, and have the specificity required for screening chemical libraries for novel protease inhibitors in a high-throughput screening assay environment. These assays have been demonstrated for enterokinase, caspase-3/7, and β-secretase.
We create long polymer nanotubes by directly pulling on the membrane of polymersomes using either optical tweezers or a micropipette. The polymersomes are composed of amphiphilic diblock copolymers, and the nanotubes formed have an aqueous core connected to the aqueous interior of the polymersome. We stabilize the pulled nanotubes by subsequent chemical cross-linking. The cross-linked nanotubes are extremely robust and can be moved to another medium for use elsewhere. We demonstrate the ability to form networks of polymer nanotubes and polymersomes by optical manipulation. The aqueous core of the polymer nanotubes together with their robust character makes them interesting candidates for nanofluidics and other applications in biotechnology.
A modeling algorithm is presented to compute simultaneously polymer conformations and ionic current, as single polymer molecules undergo translocation through protein channels. The method is based on a combination of Langevin dynamics for coarse-grained models of polymers and the Poisson–Nernst–Planck formalism for ionic current. For the illustrative example of ssDNA passing through the α-hemolysin pore, vivid details of conformational fluctuations of the polymer inside the vestibule and β-barrel compartments of the protein pore, and their consequent effects on the translocation time and extent of blocked ionic current are presented. In addition to yielding insights into several experimentally reported puzzles, our simulations offer experimental strategies to sequence polymers more efficiently.
We report that previous polymer chain scission experiments in strong flows, long analyzed according to accepted laminar flow scission theories, were in fact affected by turbulence. We reconcile existing anomalies between theory and experiment with the hypothesis that the local stress at the Kolmogorov scale generates the molecular tension leading to polymer covalent bond breakage. The hypothesis yields a universal scaling for polymer scission in turbulent flows. This surprising reassessment of over 40 years of experimental data simplifies the theoretical picture of polymer dynamics leading to scission and allows control of scission in commercial polymers and genomic DNA.
Excessive activation of the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) plays a prominent role in various of models of cellular injury. Here, we identify poly(ADP-ribose) (PAR) polymer, a product of PARP-1 activity, as a previously uncharacterized cell death signal. PAR polymer is directly toxic to neurons, and degradation of PAR polymer by poly(ADP-ribose) glycohydrolase (PARG) or phosphodiesterase 1 prevents PAR polymer-induced cell death. PARP-1-dependent, NMDA excitotoxicity of cortical neurons is reduced by neutralizing antibodies to PAR and by overexpression of PARG. Neuronal cultures with reduced levels of PARG are more sensitive to NMDA excitotoxicity than WT cultures. Transgenic mice overexpressing PARG have significantly reduced infarct volumes after focal ischemia. Conversely, mice with reduced levels of PARG have significantly increased infarct volumes after focal ischemia compared with WT littermate controls. These results reveal PAR polymer as a signaling molecule that induces cell death and suggests that interference with PAR polymer signaling may offer innovative therapeutic approaches for the treatment of cellular injury.
Apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase, is released into the cytoplasm to induce cell death in response to poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) activation. How PARP-1 activation leads to AIF release is not known. Here we identify PAR polymer as a cell death signal that induces release of AIF. PAR polymer induces mitochondrial AIF release and translocation to the nucleus. PAR glycohydrolase, which degrades PAR polymer, prevents PARP-1-dependent AIF release. Cells with reduced levels of AIF are resistant to PARP-1-dependent cell death and PAR polymer cytotoxicity. These results reveal PAR polymer as an AIF-releasing factor that plays important roles in PARP-1-dependent cell death.
In recent decades, fuel cell technology has been undergoing revolutionary developments, with fundamental progress being the replacement of electrolyte solutions with polymer electrolytes, making the device more compact in size and higher in power density. Nowadays, acidic polymer electrolytes, typically Nafion, are widely used. Despite great success, fuel cells based on acidic polyelectrolyte still depend heavily on noble metal catalysts, predominantly platinum (Pt), thus increasing the cost and hampering the widespread application of fuel cells. Here, we report a type of polymer electrolyte fuel cells (PEFC) employing a hydroxide ion-conductive polymer, quaternary ammonium polysulphone, as alkaline electrolyte and nonprecious metals, chromium-decorated nickel and silver, as the catalyst for the negative and positive electrodes, respectively. In addition to the development of a high-performance alkaline polymer electrolyte particularly suitable for fuel cells, key progress has been achieved in catalyst tailoring: The surface electronic structure of nickel has been tuned to suppress selectively the surface oxidative passivation with retained activity toward hydrogen oxidation. This report of a H2–O2 PEFC completely free from noble metal catalysts in both the positive and negative electrodes represents an important advancement in the research and development of fuel cells.
Smart materials that can respond to external stimuli are of widespread interest in biomedical science. Thermal-responsive shape memory polymers, a class of intelligent materials that can be fixed at a temporary shape below their transition temperature (Ttrans) and thermally triggered to resume their original shapes on demand, hold great potential as minimally invasive self-fitting tissue scaffolds or implants. The intrinsic mechanism for shape memory behavior of polymers is the freezing and activation of the long-range motion of polymer chain segments below and above Ttrans, respectively. Both Ttrans and the extent of polymer chain participation in effective elastic deformation and recovery are determined by the network composition and structure, which are also defining factors for their mechanical properties, degradability, and bioactivities. Such complexity has made it extremely challenging to achieve the ideal combination of a Ttrans slightly above physiological temperature, rapid and complete recovery, and suitable mechanical and biological properties for clinical applications. Here we report a shape memory polymer network constructed from a polyhedral oligomeric silsesquioxane nanoparticle core functionalized with eight polyester arms. The cross-linked networks comprising this macromer possessed a gigapascal-storage modulus at body temperature and a Ttrans between 42 and 48 °C. The materials could stably hold their temporary shapes for > 1 year at room temperature and achieve full shape recovery ≤ 51 °C in a matter of seconds. Their versatile structures allowed for tunable biodegradability and biofunctionalizability. These materials have tremendous promise for tissue engineering applications.
Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as “plastic antidotes.” Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge, and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and the creation of a “corona” of proteins around NPs that can alter and or suppress the intended performance. Here, we report the design rationale of a plastic antidote for in vivo applications. Optimizing the choice and ratio of functional monomers incorporated in the NP maximized the binding affinity and capacity toward a target peptide. Biocompatibility tests of the NPs in vitro and in vivo revealed the importance of tuning surface charge and hydrophobicity to minimize NP toxicity and prevent aggregation induced by nonspecific interactions with plasma proteins. The toxin neutralization capacity of NPs in vivo showed a strong correlation with binding affinity and capacity in vitro. Furthermore, in vivo imaging experiments established the NPs accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver. These results provide a platform to design plastic antidotes and reveal the potential and possible limitations of using synthetic polymer nanoparticles as plastic antidotes.
Lignins are complex phenylpropanoid polymers mostly associated with plant secondary cell walls. Lignins arise primarily via oxidative polymerization of the three monolignols, p-coumaryl, coniferyl, and sinapyl alcohols. Of the two hydroxycinnamyl alcohols that represent incompletely methylated biosynthetic products (and are not usually considered to be monolignols), 5-hydroxyconiferyl alcohol is now well established as incorporating into angiosperm lignins, but incorporation of caffeyl alcohol has not been shown. We report here the presence of a homopolymer of caffeyl alcohol in the seed coats of both monocot and dicot plants. This polymer (C-lignin) is deposited to high concentrations in the seed coat during the early stages of seed development in the vanilla orchid (Vanilla planifolia), and in several members of the Cactaceae. The lignin in other parts of the Vanilla plant is conventionally biosynthesized from coniferyl and sinapyl alcohols. Some species of cacti contain only C-lignin in their seeds, whereas others contain only classical guaiacyl/syringyl lignin (derived from coniferyl and sinapyl alcohols). NMR spectroscopic analysis revealed that the Vanilla seed-coat polymer was massively comprised of benzodioxane units and was structurally similar to the polymer synthesized in vitro by peroxidase-catalyzed polymerization of caffeyl alcohol. CD spectroscopy did not detect any optical activity in the seed polymer. These data support the contention that the C-lignin polymer is produced in vivo via combinatorial oxidative radical coupling that is under simple chemical control...
Nanostructured materials based on colloidal particles embedded in a polymer network are used in a variety of applications ranging from nanocomposite rubbers to organic-inorganic hybrid solar cells. Further, polymer-network-mediated colloidal interactions are highly relevant to biological studies whereby polymer hydrogels are commonly employed to probe the mechanical response of living cells, which can determine their biological function in physiological environments. The performance of nanomaterials crucially relies upon the spatial organization of the colloidal particles within the polymer network that depends, in turn, on the effective interactions between the particles in the medium. Existing models based on nonlocal equilibrium thermodynamics fail to clarify the nature of these interactions, precluding the way toward the rational design of polymer-composite materials. In this article, we present a predictive analytical theory of these interactions based on a coarse-grained model for polymer networks. We apply the theory to the case of colloids partially embedded in cross-linked polymer substrates and clarify the origin of attractive interactions recently observed experimentally. Monte Carlo simulation results that quantitatively confirm the theoretical predictions are also presented.
A number of exotic structures have been formed through high-pressure chemistry, but applications have been hindered by difficulties in recovering the high-pressure phase to ambient conditions (i.e., one atmosphere and 300 K). Here we use dispersion-corrected density functional theory [PBE-ulg (Perdew-Burke-Ernzerhof flavor of DFT with the universal low gradient correction for long range London dispersion)] to predict that above 60 gigapascal (GPa) the most stable form of N2O (the laughing gas in its molecular form) is a one-dimensional polymer with an all-nitrogen backbone analogous to cis-polyacetylene in which alternate N are bonded (ionic covalent) to O. The analogous trans-polymer is only 0.03∼0.10 eV/molecular unit less stable. Upon relaxation to ambient conditions, both polymers relax below 14 GPa to the same stable nonplanar trans-polymer. The predicted phonon spectrum and dissociation kinetics validates the stability of this trans-poly-NNO at ambient conditions, which has potential applications as a type of conducting nonlinear optical polymer with all-nitrogen chains and as a high-energy oxidizer for rocket propulsion. This work illustrates in silico materials discovery particularly in the realm of extreme conditions (very high pressure or temperature).
The way microorganisms swim in concentrated polymer solutions has important biomedical implications, i.e., how pathogens invade the mucosal lining of mammal guts. Physicists are also fascinated by self-propulsion in such complex non-Newtonian fluids. The current standard model of how bacteria propelled by rotary helical flagella swim through concentrated polymer solutions postulates bacteria-sized pores, allowing them relative easy passage. Our experiments using high-throughput methods overturn this standard model. Instead, we show that the peculiarities of flagellated bacteria locomotion in concentrated polymer solutions are due to the fast-rotating flagellum, giving rise to a lower local viscosity in its vicinity. The bacterial flagellum is therefore a nano-rheometer for probing flows at the molecular level.
Poly-l-lysine and hexadimethrine bromide (polybrene) are cationic polymers which are frequently used to enhance the transduction efficiency of recombinant retroviruses in gene therapy experiments. Conversely, chondroitin sulfate proteoglycan is an anionic polymer endogenously present in retrovirus stocks which inhibits transduction efficiency. An experimental study was performed to determine the mechanisms of retrovirus transduction modulation by these charged polymers, and it was found that they were capable of increasing or decreasing the flux of virus particles onto the cell surface. These effects, and adsorption in general, were independent of the cellular receptor-virus envelope interaction which was believed to provide the driving force for initial virus attachment. In order to consider the feasibility of alternative driving forces for virus attachment, a mathematical model of adsorption was constructed taking into account the electrostatic properties of the system. The model predicted that either cationic polymer-mediated virus aggregation or membrane charge shielding could yield adsorption phenomenon consistent with the previous observations. An experimental study was undertaken to distinguish between these two potential mechanisms...
Developing materials that interact effectively with surrounding tissue is a major obstacle in sensor and drug delivery research. The body's natural immune response prevents foreign objects from easily integrating with an organism. Without an intimate link between a biomedical device and the proximate environment, reliable measurements or delivery of molecules is not possible. Many of the current materials used for biomedical applications are centered on inert substances and polymers that degrade in the body but have limited functional capabilities. This thesis work addresses the need to develop materials that are capable of interacting in biological environments. Polypyrrole (PPy) is a conducting polymer that is a promising biomaterial for drug delivery and sensing applications. Because PPy is a polymer that can be made in degradable forms and because it can be stimulated electrically, it is an interactive platform for biomedical applications. By accomplishing the following research objectives, this thesis work could help develop an effective polymeric paradigm for tissue interactions: 1) Develop a new method to effectively micro-pattern electrodeposited polymers and metals for in vivo devices 2) Determine the optimal synthesis conditions of the conductive polymer...