Browsing by Subject "Copolymer"

Now showing 1 - 3 of 3
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    Copolymer-based membrane stabilizers for Duchenne Muscular Dystrophy
    (2016-04) Houang, Evelyne
    The overarching objective of this work centers on a structure-function approach to investigate the mechanism of action of synthetic copolymer-based membrane stabilization in the context of Duchenne Muscular Dystrophy (DMD). The guiding theme is the investigation of mechanism of interaction of membrane stabilizing copolymers using cellular and whole animal physiology, chemical engineering, and supercomputational approaches. DMD is an X-linked recessive disease of marked striated muscle deterioration affecting 1 in 3500-5000 boys. DMD results from the lack of the cytoskeletal protein dystrophin, which is essential for maintaining the structural integrity of the muscle cell membrane. DMD patients develop severe skeletal muscle degeneration, along with clinically significant cardiomyopathy. There is no cure for DMD patients, or any effective treatment to halt, prevent or reverse DMD striated muscle deterioration. The primary pathophysiological defect in DMD is the marked susceptibility to contraction-induced membrane stress and the subsequent muscle damage and degeneration that occurs due to loss of muscle membrane barrier function. In this context, a unique therapeutic approach is the use of synthetic membrane stabilizers to prevent muscle damage by directly stabilizing the dystrophin-deficient muscle membrane. The triblock copolymer poloxamer 188 (P188) has numerous features that make it an attractive synthetic membrane stabilizer candidate for DMD treatment and has been demonstrated to target and stabilize damaged membranes in various pathophysiological contexts. The efficacy of P188 in protecting the dystrophic myocardium has been well established, but its effect on the dystrophic skeletal muscle has remained unclear. This work for the first time demonstrates that P188 stabilizes the dystrophic skeletal muscle membrane in vivo and protects it against the mechanical stress associated with lengthening contractions. This result validates P188 as a therapeutic strategy to directly target the hallmark of DMD: impaired membrane stability in all striated muscles. Very little is known on how P188 interacts with and stabilizes biological membranes. To fundamentally probe the mechanism of action of synthetic copolymers as membrane stabilizers, a structure-function approach was undertaken. The aim was to gain insight into the essential critical chemical parameters of copolymers in terms of membrane interacting properties. This work shows for the first time that copolymer mass, composition, architecture, and functional end group chemistries significantly define mechanism of action at the membrane. Based on these insights, an “anchor and chain” model is advanced whereby membrane interaction is critically dependent on end group hydrophobicity. Finally, leveraging the power of supercomputational approaches, Molecular Dynamics simulations were developed to further evaluate and understand copolymer-membrane interactions at atom level resolution. Using increases in surface tension applied to the lipid bilayer, an area-per- lipid dependence of adsorption vs. insertion was uncovered, supporting the hypothesis that copolymers insert into areas of decreased lipid density and then are “squeezed-out” once membrane integrity is restored. Collectively, these findings shed new light on block copolymer dynamic interaction with biological membranes.
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    End-Effects in Diblock Copolymer Melts
    (2018-01) Mackey, Mark
    Modern understanding of block copolymer systems relies heavily on coarse-grained models and mean-field theories such as self-consistent field theory (SCFT) and Fredrickson-Helfand (FH) theory. These models simplify the system, ignoring the finer structural details of the underlying polymers. One often ignored detail is the difference in the chemistry of the last monomer on the chain. Polymer synthesis re- quires the end-monomer to have a different chemistry than the other monomers in the chain. The effect that this difference has on equilibrium properties of the system has not been thoroughly explored. This work is an attempt to quantify these effects using course-grained simulations. We report on a number of simulation measurements designed to characterize the local environment of the end-monomer. The local composition distributions of monomers around the end-monomer was measured and compared to the other monomers. Additionally the composition profile of all monomer types was measured and compared to 1-dimensional SCFT simulations. Our second focus was to quantify the shift in position of the Order-Disorder Tran- sition (ODT) due to an end-monomer that was more repulsive than the other beads in the chain. Upper and lower bounds on the new position of the ODT were calculated using conventional scattering structure factor hysteresis loop methods. A subsequent Claperyon-style approximation of the new position of the ODT agreed nicely with the range that was measured. The precise location of the ODT was then obtained using well-tempered metadynamics simulations. Finally, we estimated the effective interaction parameter χe by fitting disordered phase scattering measurements to Renormalized One Loop (ROL) theory predictions. This was used to determine the effect that the repulsive end-monomer had on the value χeN at the ODT. Our results indicate that the effect is small enough to go unnoticed when the calibration of χe is constrained to scattering data from a single chain-length.
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    Structure-Property Relationships in Poly(lactide)-based Triblock and Multiblock Copolymers
    (2016-02) Panthani, Tessie
    Replacing petroleum-based plastics with alternatives that are degradable and synthesized from annually renewable feedstocks is a critical goal for the polymer industry. Achieving this goal requires the development of sustainable analogs to commodity plastics which have equivalent or superior properties (e.g. mechanical, thermal, optical etc.) compared to their petroleum-based counterparts. This work focuses on improving and modulating the properties of a specific sustainable polymer, poly(lactide) (PLA), by incorporating it into triblock and multiblock copolymer architectures. The multiblock copolymers in this work are synthesized directly from dihydroxy-terminated triblock copolymers by a simple step-growth approach: the triblock copolymer serves as a macromonomer and addition of stoichiometric quantities of either an acid chloride or diisocyanate results in a multiblock copolymer. This work shows that over wide range of compositions, PLA-based multiblock copolymers have superior mechanical properties compared to triblock copolymers with equivalent chemical compositions and morphologies. The connectivity of the blocks within the multiblock copolymers has other interesting consequences on properties. For example, when crystallizable poly(l-lactide)-based triblock and multiblock copolymers are investigated, it is found that the multiblock copolymers have much slower crystallization kinetics. Additionally, the total number of blocks connected together is found to eect the linear viscoelastic properties as well as the alignment of lamellar domains under uniaxial extension. Finally, the synthesis and characterization of pressure-sensitive adhesives based upon renewable PLA-containing triblock copolymers and a renewable tackifier is detailed. Together, the results give insight into the effect of chain architecture, composition, and morphology on the mechanical behavior, thermal properties, and rheological properties of PLA-based materials.