Interactions governing the self-assembly of globular protein-polymer block copolymers
Author(s)Lam, Christopher N. (Christopher Nguyen)
Massachusetts Institute of Technology. Department of Chemical Engineering.
Bradley D. Olsen.
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Engineering enzymes and other proteins into biocatalysts or bioelectronic devices has the potential to lead to a new generation of energy-generating and energy conversion technologies. Controlling the hierarchical structure of protein materials from the nanoscale single molecule level up to the microscale material morphology is critical to improving their function. Lithographic patterning methods such as electron beam lithography, dip-pen nanolithography, and nanograftin allow proteins to be patterned with nanoscale resolution, but parallelization to increase throughput remains a significant challenge. While templated self-assembly enables patterning in three dimensions, maximizing protein loading and controlling orientation are challenges that remain to be addressed. Self-assembly provides a low-cost method to nanopattern proteins for biofunctional devices with high operational efficiency through control over three-dimensional spatial arrangement and orientation. Complementary experimental techniques were used to investigate the phase behaviors of globular protein-polymer block copolymers and provide insight into the relevant physics and thermodynamics governing their self-assembly. In particular, methodical permutations were made to the protein block to understand the relationship between protein interactions and protein-polymer block copolymer selfassembly. Order-disorder and order-order transitions were demonstrated for the first time within a rich window of phase space of hexagonal, lamellar, perforated lamellar, and micellar phases that were dependent on coil fraction. Protein-polymer net repulsive interactions were discovered to be important for self-assembly. The type of nanostructures formed at a given coil fraction are different between globular-coil and coil-coil systems due to the anisotropy between protein and coil shape and interactions and minor differences in solvent selectivity. A set of structurally homologous proteins in which the chemical composition and surface interaction potential were varied globally throughout the entire sequence and locally through single point mutations demonstrated highly similar phase behavior, revealing that coarse-grained properties such as the protein shape, size, solubility, surface charge, and virial coefficient can capture the general shape of the phase diagram in nonselective solvents. Engineering greater changes in protein electrostatic interactions and virial coefficient demonstrated that the electrostatic environment of proteins may be designed to tune the morphologies of protein-polymer blok copolymers, both enhancing and suppressing formation of nanostructures through attractive and repulsive interactions, respectively. A combination of small-angle neutron scattering experiments, theory, and coarse-grained modeling and simulation was used to elucidate the shape of protein-polymer block copolymers in dilute solution and quantify their interactions. Modeling protein-polymer interactions using repulsive Weeks-Chandler- Andersen potentials showed that the polymer exists as a relatively unperturbed coil extended away from the protein. The coarse-grained representation additionally provides a simple way to model the conformation of protein-polymer conjugates with strong interactions that result in the polymer wrapping around the protein in a shroud-like configuration.
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2016.Cataloged from PDF version of thesis.Includes bibliographical references.
DepartmentMassachusetts Institute of Technology. Department of Chemical Engineering.
Massachusetts Institute of Technology