Structural and Mechanical Characteristics of Polymersomes
Date Issued
2014
Date
2014
Author(s)
Chang, Hung-Yu
Abstract
Polymersomes self-assembled from amphiphilic macromolecules have attracted a growing attention because of their multifunctionality and stability. By controlling the structural characteristics of polymersomes, including vesicle shape, size, and membrane thickness, the mechanical and transport properties as well as the fusion behavior of a polymersome can be manipulated. Numerous experimental techniques have been developed to explore polymersome characteristics; however, experimental microscopic observations and knowledge of vesicles are limited. Mesoscale simulations can complement experimental studies of the vesicular features at the microscopic level and thus provide a feasible method to better understand the relationship between the fundamental structures and physicochemical properties of a polymersome. Moreover, the predictive ability of the simulation approaches may greatly assist developments and future applications of polymersomes. This dissertation uses dissipative particle dynamics (DPD) to explore the self-assembly of three polymeric systems. A series of morphological phase diagrams of polymers with different topological structures have been constructed. In addition, we have paid particular attention to the fundamental properties of polymersomes and their biological behaviors. There are three parts in this dissertation. The first part (Chapter 3) investigates the self-assembly of polymer brushes consisting of a solvophobic backbone attached with two different side chains, solvophilic and amphiphilic diblock. Dependent on the block length, molecular architecture, and grafting density, the multicompartment aggregate exhibits a rich variety of morphological conformations, including five types of vesicles, porous aggregates, worm-like micelles, donut micelles, hamburger micelles, and unimolecular micelles. For certain polymer brushes, atypical polymersomes with asymmetric multilayered membranes are spontaneously formed. Moreover, temperature variation induced morphological transformation from an asymmetric four-layered polymersome to a symmetric seven-layered polymersome is observed for polymer brushes containing a thermoresponsive block. Consequently, the resulting polymersome decreases in size quite sharply as temperature exceeds lower critical solution temperature. These simulation findings are consistent with experimental observations. At a fixed composition of polymer brushes, the aggregate morphology varies with the structural arrangement of the two solvophilic blocks in the molecule. Asymmetric polymersomes are formed when the two solvophilic blocks are separately attached to the backbone and side chain. Although asymmetric vesicles are observed at moderate grafting density, unique donut aggregates are formed for high density but hamburger micelles develop at low density. In the second part (Chapter 4), the self-assembly behavior of amphiphilic comb-like graft copolymers bearing pH-responsive hydrophilic side chains on hydrophobic backbone in a selective solvent is studied. The aggregate exhibits a rich variety of the morphological conformations dependent on pH, polymeric concentration, side chain length, and grafting density. The morphological phase diagram shows that micellar aggregates take shape at low pH. As pH increases, unilamellar vesicle (ULV) can form at low polymer concentration and the vesicle size grows with increasing concentration. Further increment of pH to neutral leads to the formation of multilamellar vesicles (MLV) with the layer-by-layer structure similar to that of an onion. The total number of layers rises with increasing polymer concentration. Our simulation outcomes are consistent with the experimental observations. The simulation results also reveal that as the grafting density is decreased, the thickness of the hydrophobic layer grows and thus the total number of layers declines for MLVs. The water permeation process through ULV descends as the grafting density is decreased or the neutral pH is approached. Controlled releases of two types of drugs with different hydrophobicity situated at different layers of MLV are also examined. The release rate of hydrophilic drug is faster than that of hydrophobic drug. Polymersomes tend to fuse but the fusion mechanism is different from that of liposomes. The fusion pathway of ULVs follows the anisotropic stalk-pore scenario and both stalk and pore formation prefer to occur on the edge of the contact zone due to significant deformations of comb-like polymers in this region. The fusion pathway of MLVs is layer-by-layer and the fusion time of the inner layer is faster than that of the outer layer. The fusion process is expedited at about neutral pH but is prolonged substantially as the side chain length is increased. Finally, it is interesting to observe that the total number of layers of the fused MLV can be greater than that of MLVs before fusion. In the third part (Chapter 5), the self-assembly behavior of polymer-tethered nanoballs (NBs) with nonpolar/polar/ nonpolar (n-p-n'')motif in a selective solvent is investigated. A model NB bears two hydrophobic polymeric arms (n''-part) tethered on an extremely hydrophobic NB (n-part) with hydrophilic patch (p-part) patterned on its surface. Dependent on the hydrophobicity and length of tethered arms, three types of aggregates are exhibited, including NB vesicle, core-shell micelle, and segmented-worm. NB vesicles are developed for a wide range of hydrophobic arm lengths. The presence of tethered arms perturbs the bilayer structure formed by NBs. The structural properties including the order parameter, membrane thickness, and area density of the inner leaflet decrease with increasing the arm length. These results indicate that for NBs with longer arms, the extent of interdigitation in the membrane rises so that the overcrowded arms in the inner corona are relaxed. The transport and mechanical properties are evaluated as well. As the arm length grows, the permeability increases significantly because the steric bulk of tethered arms loosens the packing of NBs. By contrast, the membrane tension decreases owing to the reduction of NB/solvent contacts by the polymer corona. Although fusion can reduce membrane tension, NB vesicles show strong resistance to fusion. Moreover, the size-dependent behavior observed in small liposomes is not significant for NB vesicles due to isotropic geometry of NB.
Subjects
amphiphilic polymer
self-assembly
dissipative particle dynamics (DPD)
polymersome
stimuli responsiveness
Type
thesis
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