Interaction of Daptomycin with Lipid Bilayers Correlated to Its Action on Cell Membranes

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dc.contributor.advisorHuang, Huey W.en_US
dc.contributor.committeeMemberToffoletto, Frank R.en_US
dc.contributor.committeeMemberKillian, Thomas C.en_US
dc.creatorChen, Yen-Feien_US
dc.date.accessioned2014-08-07T20:07:09Zen_US
dc.date.available2014-08-07T20:07:09Zen_US
dc.date.created2013-12en_US
dc.date.issued2013-05-31en_US
dc.date.submittedDecember 2013en_US
dc.date.updated2014-08-07T20:07:10Zen_US
dc.description.abstractDaptomycin is a lipopeptide antibiotic notably against multidrug-resistant, gram-positive pathogens. Evidence shows that the antibiotic acts neither on DNA nor on the proteins. It has been shown to insert and aggregate in the bacteria membrane; nevertheless, how the molecular interaction leads to cell death is unknown. In this work, the physical properties of interactions between daptomycin and model membranes are studied in order to understand the underlying mechanism of daptomycin. First, daptomycin’s binding affinity to membranes was found to be proportional to Ca++ concentration. The effect of Ca++ cannot be replaced by other divalent ions such as Mg++. After binding, daptomycin was found to form lipid-peptide aggregations on phosphatidylglycerol(PG)-containing vesicles. PG is required for the formation of lipid-peptide aggregates, which eventually lead to membrane ruptures. Cardiolipin, another main component in bacterial membrane, cannot substitute PG to induce the same membrane defect. In addition, with a fixed concentration of Ca++, it requires a minimum concentration of daptomycin to trigger the membrane defect process. The membrane defect results mainly from lipid-peptide aggregations rather than from pores forming in the membrane. Finally, x-ray data imply that daptomycin binds to the headgroup region of the bilayer, which causes membrane thinning. The elastic energy of membrane thinning elevates the energy level of the daptomycin binding state, which explains the transition to the aggregation state.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationChen, Yen-Fei. "Interaction of Daptomycin with Lipid Bilayers Correlated to Its Action on Cell Membranes." (2013) Master’s Thesis, Rice University. <a href="https://hdl.handle.net/1911/76483">https://hdl.handle.net/1911/76483</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/76483en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectMembraneen_US
dc.subjectDaptomycinen_US
dc.subjectAntimicrobial peptidesen_US
dc.subjectGUVen_US
dc.titleInteraction of Daptomycin with Lipid Bilayers Correlated to Its Action on Cell Membranesen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentPhysics and Astronomyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelMastersen_US
thesis.degree.nameMaster of Scienceen_US
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