FEATURES OF IN SITU FORMATION OF MIXTURES OF LINEAR POLYMERS

This article is devoted to the analysis of the results of the investigation of the process of forming mixtures of linear polymers formed simultaneously in situ according to different mechanisms. The first mechanism is polyaddition, the second mechanism is radical polymerization. This is one of the possible ways to obtain multicomponent polymer systems. The kinetics of chemical reactions of the formation of components and the phase separation which accompanies these reactions were studied for mixtures of poly(methyl methacrylate) (PMMA) with two polyurethanes (PU) of different chemical nature of both flexible and rigid blocks. PU-1 was synthesized from macrodiisocyanate based on oligo(tetramethylene glycol) with molecular mass 1000 g·mol–1 and hexamethylene diisocyanate taken in the molar ratio 1 : 2 using diethylene glycol as a chain extender. PU-2 was synthesized from macrodiisocyanate based on olygo(propylene glycol) with molecular mass 1000 g·mol–1 and toluylene diisocyanate taken in the molar ratio 1 : 2 using butanediol as a chain extender. The mixture of polystyrene (PS) with PU-2 was studied too. It is established that regardless of the chemical nature of the components, the process of in situ mixture formation is subject to general laws. In particular, the change in the chemical nature of the component formed by the mechanism of polyaddition (mixtures PMMA/PU-1 and PMMA/PU-2) or of the component formed by radical polymerization (mixtures PMMA/PU-2 and PS/PU-2) does not affect the nature of the dependence of the conversion degree of components and the fraction of formed polymers at the beginning of the phase separation on the composition of the initial reaction mixtures. Only the absolute values of these parameters change due to different reactivity and different thermodynamic compatibility of the mixed components.

Mucus threads from surface goblet cells clear particles from the airways

Background The mucociliary clearance system driven by beating cilia protects the airways from inhaled microbes and particles. Large particles are cleared by mucus bundles made in submucosal glands by parallel linear polymers of the MUC5B mucins. However, the structural organization and function of the mucus generated in surface goblet cells are poorly understood. Methods The origin and characteristics of different mucus structures were studied on live tissue explants from newborn wild-type (WT), cystic fibrosis transmembrane conductance regulator (CFTR) deficient (CF) piglets and weaned pig airways using video microscopy, Airyscan imaging and electron microscopy. Bronchoscopy was performed in juvenile pigs in vivo. Results We have identified a distinct mucus formation secreted from the surface goblet cells with a diameter less than two micrometer. This type of mucus was named mucus threads. With time mucus threads gathered into larger mucus assemblies, efficiently collecting particles. The previously observed Alcian blue stained mucus bundles were around 10 times thicker than the threads. Together the mucus bundles, mucus assemblies and mucus threads cleared the pig trachea from particles. Conclusions These results demonstrate that normal airway mucus is more complex and has a more variable structural organization and function than was previously understood. These observations emphasize the importance of studying young objects to understand the function of a non-compromised lung.

The C. albicans virulence factor Candidalysin polymerizes in solution to form membrane pores and damage epithelial cells.

The pathogenic fungus Candida albicans causes severe invasive candidiasis. C. albicans infection requires the action of the virulence factor Candidalysin (CL), which damages the plasma membrane of the target human cells. However, the molecular mechanism that CL uses to permeabilize membranes is poorly understood. We employed complementary biophysical, modeling, microscopy, and cell biology methods to reveal that CL forms membrane pores using a unique molecular mechanism. Unexpectedly, it was observed that CL readily assembles into linear polymers in solution. The basic structural unit in polymer formation is a CL 8-mer, which is sequentially added into a string configuration. Finally, the linear polymers can close into a loop. Our data indicate that CL loops spontaneously insert into the membrane to become membrane pores. We identified a CL mutation (G4W) that inhibited the formation of polymers in solution and prevented formation of pores in different synthetic lipid membranes systems. Studies in epithelial cells showed that G4W CL failed to activate the danger response signaling pathway, a hallmark of the pathogenic effect of CL. These results indicate that CL polymerization in solution is a necessary step for the damage of cellular membranes. Analysis of thousands of CL pores by atomic force microscopy revealed the co existence of simple depressions and complex pores decorated with protrusions. Imaging and modeling indicate that the two types of pores are formed by CL molecules assembled into alternate orientations. We propose that this structural rearrangement represents a maturation mechanism that might stabilize pore formation to achieve more robust cellular damage. Taken together, the data show that CL uses a previously unknown mechanism to damage membranes, whereby pre-assembly of CL loops in solution directly leads to formation of membrane pores. Our investigation not only unravels a new paradigm for the formation of membrane pores, but additionally identifies CL polymerization as a novel therapeutic target to treat candidiasis.

Rheo-NMR Investigations of Flow and Alignment in Complex Fluids

<p>This thesis reports the use of Rheo-NMR, that is, a class of techniques within the realm of magnetic resonance which are both confirmatory and complementary to rheometric experiments on materials which can best be classified as complex fluids. The physical properties of such fluids are both hybrid and, in general, vaguely defined. In displaying characteristics attributable to both ideal fluids and elastic solids, the term `complex fluid', in a very real sense, epitomises all the fluids with which every human deals with (and is comprised of) daily. With a multitude of potential candidates for further research then, here we confine ourselves to fluids of molecules and aggregates which are either linear polymers or at least maintain the curvilinear one-dimensional topology of linear polymers. Magnetic resonance is an ideal research tool in this regard, as it is in many respects a rather statistical and insensitive tool from a signal-to-samplevolume perspective, precisely the regime in which the dynamics of a macroscopic collection of macromolecules is relevant. Material deformation is the mechanism upon which rheological measurement depends, and the first research presented here reports on a numerical simulation of the NMR signal of sheared polymer melts. Proton NMR relaxation times of such melts have previously been measured experimentally and found to depend on the shear rate applied by a horizontal Couette geometry, presumably due to the alignment of the mean-field boundaries of the space in which the polymer may reside, known as the polymer tube. The restrictions forming the tube are the other polymers in the bulk, around which an exemplar polymer molecule must meander. In diffusing through this tube, whose direction between entanglements is random in equilibrium, at any time, the return-to-origin correlation for a single spin returning to its locally anisotropic environment generates the least NMR transverse relaxation, as the sum contribution from all tube segments is random. When a deformation-related transformation matrix is applied to the coordinates of entanglements in the polymer, tube segments are no longer isotropically distributed, and an enhanced relaxation process results. Here we present the results of a numerical simulation of this procedure, based on the earlier model of Ball, Callaghan and Samulski, in addition to measurements of the transverse NMR relaxation by Cormier. Not only does it demonstrate qualitative agreement, the NMR signal can be simulated quantitavely or conversely, the size of several key polymer physics parameters can be found through fitting to the NMR signal. Proton NMR spectroscopy is inherently simpler than deuteron NMR spectroscopy, in which the nucleus of interest is quadrupolar. However, a large section of this thesis deals with the structures and response of worm-like micellar structures in solution, for which alignment data cannot reasonably be measured with the proton alone. The most used sample in this thesis is that of the BASF nonionic block copolymer Pluronic P105 in aqueous solution (5% w/w), and a small amount of 1-phenylethanol is required to stabilise cylindrical micellar structures. 1-phenylethanol is a small molecule perfectly suited to act also as a deuterated probe molecule to observe alignment, as it resides in the core of the micelle. By using a variety of Rheo-NMR techniques, such as velocimetry, spatially resolved spectroscopy, and diffusometry, many different flow and alignment behaviours were observed for this solution in Couette flow. Following the measured temperature-dependent viscosity of the P105 solution, which shows an elevated viscosity in a temperature region 15K wide centred at 297 K, we use temperature and applied shear rate as independent variables in our experiments, first identifying spectral features through diffusometry, and then observing a range of behaviours including shear-banding and quadrupolar splitting indicating alignment. Finally we present some experimental work performed in the extensional flow geometry known as the semi-hyperbolic converging die. Extensional flow, inherently, is a transient and nite procedure, and such a geometry is designed to produce a constant extension rate along the axis of its constricting pipe, which, compared to the mill geometries, improves the volume and time over which extension occurs. We investigate the flow and alignment measuring capabilities of Rheo-NMR in this geometry.</p>

Rheo-NMR Investigations of Flow and Alignment in Complex Fluids

<p>This thesis reports the use of Rheo-NMR, that is, a class of techniques within the realm of magnetic resonance which are both confirmatory and complementary to rheometric experiments on materials which can best be classified as complex fluids. The physical properties of such fluids are both hybrid and, in general, vaguely defined. In displaying characteristics attributable to both ideal fluids and elastic solids, the term `complex fluid', in a very real sense, epitomises all the fluids with which every human deals with (and is comprised of) daily. With a multitude of potential candidates for further research then, here we confine ourselves to fluids of molecules and aggregates which are either linear polymers or at least maintain the curvilinear one-dimensional topology of linear polymers. Magnetic resonance is an ideal research tool in this regard, as it is in many respects a rather statistical and insensitive tool from a signal-to-samplevolume perspective, precisely the regime in which the dynamics of a macroscopic collection of macromolecules is relevant. Material deformation is the mechanism upon which rheological measurement depends, and the first research presented here reports on a numerical simulation of the NMR signal of sheared polymer melts. Proton NMR relaxation times of such melts have previously been measured experimentally and found to depend on the shear rate applied by a horizontal Couette geometry, presumably due to the alignment of the mean-field boundaries of the space in which the polymer may reside, known as the polymer tube. The restrictions forming the tube are the other polymers in the bulk, around which an exemplar polymer molecule must meander. In diffusing through this tube, whose direction between entanglements is random in equilibrium, at any time, the return-to-origin correlation for a single spin returning to its locally anisotropic environment generates the least NMR transverse relaxation, as the sum contribution from all tube segments is random. When a deformation-related transformation matrix is applied to the coordinates of entanglements in the polymer, tube segments are no longer isotropically distributed, and an enhanced relaxation process results. Here we present the results of a numerical simulation of this procedure, based on the earlier model of Ball, Callaghan and Samulski, in addition to measurements of the transverse NMR relaxation by Cormier. Not only does it demonstrate qualitative agreement, the NMR signal can be simulated quantitavely or conversely, the size of several key polymer physics parameters can be found through fitting to the NMR signal. Proton NMR spectroscopy is inherently simpler than deuteron NMR spectroscopy, in which the nucleus of interest is quadrupolar. However, a large section of this thesis deals with the structures and response of worm-like micellar structures in solution, for which alignment data cannot reasonably be measured with the proton alone. The most used sample in this thesis is that of the BASF nonionic block copolymer Pluronic P105 in aqueous solution (5% w/w), and a small amount of 1-phenylethanol is required to stabilise cylindrical micellar structures. 1-phenylethanol is a small molecule perfectly suited to act also as a deuterated probe molecule to observe alignment, as it resides in the core of the micelle. By using a variety of Rheo-NMR techniques, such as velocimetry, spatially resolved spectroscopy, and diffusometry, many different flow and alignment behaviours were observed for this solution in Couette flow. Following the measured temperature-dependent viscosity of the P105 solution, which shows an elevated viscosity in a temperature region 15K wide centred at 297 K, we use temperature and applied shear rate as independent variables in our experiments, first identifying spectral features through diffusometry, and then observing a range of behaviours including shear-banding and quadrupolar splitting indicating alignment. Finally we present some experimental work performed in the extensional flow geometry known as the semi-hyperbolic converging die. Extensional flow, inherently, is a transient and nite procedure, and such a geometry is designed to produce a constant extension rate along the axis of its constricting pipe, which, compared to the mill geometries, improves the volume and time over which extension occurs. We investigate the flow and alignment measuring capabilities of Rheo-NMR in this geometry.</p>

Aliphatic Polyester Nanoparticles for Drug Delivery Systems

Drug delivery systems using aliphatic polyester nanoparticles are usually prepared via an emulsion process. These nanoparticles can control drug release and improve pharmacokinetics. Aliphatic polyesters are linear polymers containing ester linkages, showing sensitivity to hydrolytic degradation. The byproducts then promote autocatalytic degradation. These byproducts could enter the Krebs cycle and be eliminated from the body, resulting in the high biocompatibility of these nanoparticles. The properties of these polyesters are linked to the drug release rate due to biodegradation, i.e., polymer crystallinity, glass transition temperature, polymer hydrophobicity, and molecular weight (MW), all of which relatively influence hydrolysis. Mathematical equations have been used to study the factors and mechanisms that affect drug dissolution compared to experimental release data. The equations used as models for predicting the kinetics of drug release include the zero-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas equations. Aliphatic polyester-based controlled drug delivery has surrounded much of the current activity in the estimation parameters of nanoparticles and stimulated additional research. Polymeric nanoparticles have potential in a wide range of applications, such as in biotechnology, vaccine systems, and the pharmaceutical industry. The main goal of this chapter is to discuss aliphatic polyester nanoparticles as drug carrier systems.