Novel Development of Super-Resolution Force Spectroscopy and Applications in Biological Systems

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dc.contributor.advisorXu, Shoujun
dc.contributor.committeeMemberHoffman, David M.
dc.contributor.committeeMemberBrgoch, Jakoah
dc.contributor.committeeMemberYang, Ding-Shyue
dc.contributor.committeeMemberBrazdeikis, Aurdius
dc.creatorJia, Haina 1987-
dc.date.accessioned2019-05-23T14:20:12Z
dc.date.createdAugust 2018
dc.date.issued2018-08
dc.date.submittedAugust 2018
dc.date.updated2019-05-23T14:20:12Z
dc.description.abstractThis dissertation focuses on applications of new techniques that are used to investigate interactions in biological systems. Atomic magnetometry and ultrasound have been extensively used as individual techniques in various physical and engineering fields. Their combination, however, has been rare. Super-resolution force spectroscopy (SURFS) was developed based on the integration of these two techniques, and it has unique biophysical applications in studying drug-DNA interactions and ribosomal translocations. I demonstrate that SURFS has a high force resolution of 0.5 pN by resolving the dissociation forces of 12 base pairs of DNA duplex and 11 base pairs of DNA duplex with the drug daunomycin. The SURFS technique was used to determine the positions of the ribosome on the mRNA at two distinct states. I found that from the post-translocation state (Post) to the subsequent pre-translocation state (Pre), the ribosome moves spontaneously by nearly half a nucleotide. The application of SURFS was expanded in biophysics. I was able to precisely resolve three small molecules binding with two DNA sequences, which were difficult to distinguish by using previous force spectroscopic techniques. The results indicate that the differential binding forces caused by drug binding correlate with enthalpy instead of free energy, thus providing an alternative physical parameter for optimizing chemotherapeutic drugs. Force-induced visualization (FIV) can determine the functional position of nucleic acids with single-nucleotide resolution by visually distinguishable states. The use of an adjustable mechanical force overcomes the variations of buffer conditions and analyte concentrations. Probing the mRNA movement during ribosomal translocation, and revealing the interacting sites and strengths of DNA-binding drugs were investigated. The experimental setup used to record and quantify data was achieved with an affordable and portable device coupled with a smart phone. Massive detections were achieved by simultaneously using acoustic radiation force. The simplicity of the method, low cost of the device, and high efficiency of the measurements have broad applications for FIV in biomolecular research.
dc.description.departmentChemistry, Department of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10657/3992
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectSuper-resolution force spectroscopy
dc.subjectDNA-drug
dc.subjectRibosome motion
dc.subjectForce-induced visualization
dc.titleNovel Development of Super-Resolution Force Spectroscopy and Applications in Biological Systems
dc.type.dcmiText
dc.type.genreThesis
local.embargo.lift2020-08-01
local.embargo.terms2020-08-01
thesis.degree.collegeCollege of Natural Sciences and Mathematics
thesis.degree.departmentChemistry, Department of
thesis.degree.disciplineChemistry
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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