Biomedical Engineering ETDs
Publication Date
Fall 11-20-2017
Abstract
Membranes and membrane-associated components are the target of approximately 60% of the current drugs, of synthetic materials, such as polymers, which are used for drug delivery purposes and of other biomolecules, such as endotoxins, which gain entry into the cell by disrupting the membrane. Therefore, the development of biomimetic membrane assemblies allows the study of different biological processes in which cell membranes play an important role, and the characterization and screening of drug delivery tools and other membrane-bound components.
Since its development, membrane assemblies on planar silica surfaces have been the method of choice to study membrane-associated and membrane-bound components. However, the screening process of planar-substrate supported membranes has some limitations, as they rely on non-high-throughput or multiplexable technologies, like microscopy or Surface Plasmon Resonance (SPR). This results in time consuming studies, high cost, and high variability from sample to sample. Another biomimetic assembly commonly used are giant unilamellar vesicles (GUVs), which has proven to be valuable, as it better mimics the size and shape of cell membranes. Nevertheless, their assembly is time consuming and presents polydispersity.
The need of a biomimetic platform amenable to high-throughput screening process inspired the development of silica microsphere-supported membranes, as an alternative to planar-supported membranes and GUVs. Microsphere-supported membranes can be screened using flow cytometry, which is a laser-based high-throughput technology that measures several thousand particles and their physical characteristics in a few seconds. Moreover, flow cytometry has the advantage of being highly sensitive, accurate, reproducible, and it uses small sample volumes, making the screening process faster and more affordable.
To that end, we built and characterized multiplexable biomimetic membranes on silica microspheres for flow-based screening applications. Furthermore, we demonstrated that this new biomimetic construct could potentially constitute a more effective way of performing target based screening assays for membrane-bound components. We used microsphere-supported biomimetic membranes to screen: 1) membrane-protein interactions, 2) membrane disruption assays, and 3) polymer membrane interactions. Future areas for application of these methods are in areas such as, drug screening, antimicrobial peptide screening, and protease assay development.
Language
English
Keywords
multiplex biomimetic membranes, flow cytometry, microspheres
Document Type
Dissertation
Degree Name
Biomedical Engineering
Level of Degree
Doctoral
Department Name
Biomedical Engineering
First Committee Member (Chair)
Andrew P. Shreve
Second Committee Member
Steven G. Graves
Third Committee Member
Gabriel A. Montaño
Fourth Committee Member
Deborah G. Evans
Recommended Citation
Fernandez Oropeza, Nadiezda P.. "Development of biomimetic membrane assemblies on microspheres for high-throughput and multiplexable studies." (2017). https://digitalrepository.unm.edu/bme_etds/17
Included in
Biomedical Devices and Instrumentation Commons, Other Biomedical Engineering and Bioengineering Commons
