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Author ORCID Identifier

https://orcid.org/0000-0003-4274-5425

AccessType

Open Access Dissertation

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Chemical Engineering

Year Degree Awarded

2023

Month Degree Awarded

September

First Advisor

Peter J. Beltramo

Subject Categories

Biomaterials | Membrane Science | Other Chemical Engineering

Abstract

Lipids are an integral part of cells, being the principal component of the cell membrane, and contributing to the function and regulation of biological processes. Lipid nanoparticles mimicking a cell’s endosomes or exosomes are of particular interest within the pharmaceutical industry for their ability to deliver cargo such as RNA into target cells. The delivery process faces a multitude of challenges, so a rational design approach for vesicles that considers a lipid’s physicochemical contribution to the membrane is desired. To that end, this thesis explores the creation of large area biomembranes along with the development of electromechanical and optical characterization methods with the goal of determining structure-function relationships of membranes and their constituent lipids in different compositional and ionic environments. We demonstrated the ability to create large area model biomembranes (LAMBs) with control over their lipid and external ionic composition, both symmetrical and asymmetrical. We explored the Young’s modulus and bending rigidity of DOPC, DOPG symmetric and asymmetric membranes using electrostriction. This enables us to map the lipid-dependent physical property changes for bilayers, relate lipid composition to physical rearrangement such as formation of a fusion stalk, and compare them to existing literature for other platforms. The fusion process necessitates interaction between two opposing lipid monolayers; thus we use a thin film balance approach to explore headgroup-headgroup interactions. These interactions are modulated by electrostatic forces arising from two charged monolayers nearing each other, the ionic contents of the solution, and structural forces. We determine the magnitude of the electrostatic component of the film’s disjoining pressure through careful drainage. Additionally, dynamic drainage of the same films yields aggregate information of both electrostatic and structural forces within the film. Knowledge of monolayer headgroup interactions will help inform and shape the design space for vesicle-membrane fusion experiments Towards this end, we have performed experiments exploring calcium induced vesicle growth, adhesion of vesicles on the bilayer surface, and demonstrated analytical approaches to quantify deposition, growth, and fusion. Cationic lipid within the membrane promotes adhesion and retention of vesicles. The work laid out here establishes the design of vesicle-bilayer systems that can be expanded to more complex biologically relevant compositions.

DOI

https://doi.org/10.7275/35984309

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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