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IMAGING MOLECULAR TRANSPORT ACROSS AND NANOMATERIAL
INTERACTION WITH LIPID MEMBRANES
by
Su Li
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(CHEMICAL ENGINEERING)
May 2013
Copyright 2013 Su Li
Object Description
| Title | Imaging molecular transport across and nanomaterial interaction with lipid membranes |
| Author | Li, Su |
| Author email | lisu01@gmail.com;lisu01@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Chemical Engineering |
| School | Viterbi School of Engineering |
| Date defended/completed | 2012-12-12 |
| Date submitted | 2013-01-24 |
| Date approved | 2013-01-25 |
| Restricted until | 2013-01-25 |
| Date published | 2013-01-25 |
| Advisor (committee chair) | Malmstadt, Noah |
| Advisor (committee member) |
Wang, Pin Kim, Kwang-Jin |
| Abstract | The ability of a molecule to pass through the plasma membrane without the aid of any active cellular mechanisms is central to that molecule’s pharmaceutical characteristics. Passive transport has been understood in the context of Overton’s rule, which states that more lipophilic molecules cross membrane lipid bilayers more readily. Standard techniques including planar lipid membrane, liposome, and cell monolayer to observe passive transport processes are flawed and lack reproducibility. ❧ This research describes assays based on spinning-disk confocal microscopy (SDCM) of giant unilamellar vesicles (GUVs) that allow for fluorescent molecules to be tracked as they permeate the lipid membrane. This approach allows for the temporal development of the concentration field to be directly observed. Precise membrane permeability can be determined from by fitting the data to a mathematical permeation model. ❧ A series of molecules of increasing hydrophilicity was constructed by conjugating 4-nitrobenzo-2-oxa-1,3-diazole (NBD) with poly(ethylene-glycol) (PEG). An analytical passive transport model was devised, image intensity data was regressed to the model, and permeability was calculated. The result shows that longer chain PEG molecules which are more hydrophilic permeate more slowly. This trend is consistent with Overton’s rule, though it does not seem to fit a simple partition-diffusion model of membrane transport. ❧ Low-molecular-weight carboxylic acids have crucial effects on cellular processes. We studied the transport of carboxylic acids with different carbon chains lengths into GUVs. Fluorescein-dextran was used to trace the transport of acid. GUVs were immobilized on the surface of a poly(dimethylsiloxane) (PDMS) microchannel which allows the changing of buffer solution quickly and uniformly. The results showed that the permeabilities are consistent with octanol-water partition coefficients and demonstrate that Overton’s rule applies for this class of molecules. ❧ Synthetic lipid bilayers were used to study potentially harmful interactions between nanoparticles and biomembranes. Twenty nm polystyrene nanoparticles with cationic surfaces adhere strongly to lipid membranes. Adhesion is driven by nonspecific electrostatic interactions between the lipid phosphate groups and the nanoparticles. Nanoparticle adhesion leads to membrane morphological deformation and the formation of transient nanoscale pores. These results suggest that nanoparticle adhesion imposes surface tension on biomembranes via a steric crowding mechanism, leading to poration. |
| Keyword | confocal microscopy; giant unilamellar vesicle; passive membrane transport; Overton’s rule; cationic nanoparticles; membrane deformation |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Li, Su |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume6/etd-LiSu-1407.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Full text | IMAGING MOLECULAR TRANSPORT ACROSS AND NANOMATERIAL INTERACTION WITH LIPID MEMBRANES by Su Li A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (CHEMICAL ENGINEERING) May 2013 Copyright 2013 Su Li |
