Interactions of Amyloid-Forming Peptides with Lipid Bilayer Membranes

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dc.contributor.advisorHuang, Huey W.
dc.creatorLee, Chang-Chun
dc.date.accessioned2013-03-08T00:35:29Z
dc.date.available2013-03-08T00:35:29Z
dc.date.issued2012
dc.description.abstractAmyloid-proteins are among the most actively researched biological topics today, because they have been associated with many serious human diseases, such as Alzheimer's disease and type II diabetes. In particular the deposition of protein aggregates on cell membranes has been suspected as the causes of the diseases, although the proof is still elusive. Studying the interactions of amyloid-forming peptides with lipid-bilayer membranes may clarify the pathway of the β-aggregate formation and provide new insights into the amyloid hypothesis of diseases. In this thesis, I investigate how three peptides, penetratin, amylin, and LL-37, interact with lipid membranes by using several techniques well-developed in our lab. In the study of penetratin interacting with lipid membranes, we were able to clarify the energy pathway of amyloid formation mediated by membrane-binding. This provides the sole experimental proof for the Jarrett-Lansbury theory of β- amyloid formation. Our investigation on amylin-membrane interaction clarifies how amylin in different forms damage bilayer membranes. Between penetratin and amylin we have clarified the complicated pattern of interactions between amyloid-forming peptides and lipid bilayers. The third peptide LL-37 studied in my thesis turned out to a pore forming peptide. I found the mistake made by previous investigators in several different laboratories that made them erroneously conclude that LL-37 was not a pore forming peptide. The results of these three peptides show that methods we used are a comprehensive set of tools that can reveal a broad range of peptide properties. Both the formation of amyloid aggregates and formation of membrane pores can be explained by a two-state model proposed by Huang describing peptide-membrane interactions. For LL-37, the second state is a pore in membrane. But for penetratin and amylin the second state is an aggregation in the β form. We found that β-aggregates have low affinity within a lipid bilayer, and therefore exit from the bilayer structure. However, this exit process extracts lipid molecules from the bilayer and incorporates them in the peptide aggregates. We suggest that this is the molecular process of how amylin might damage of the membranes of β-cells.
dc.format.extent153 p.en_US
dc.format.mimetypeapplication/pdf
dc.identifier.callnoTHESIS PHYS. 2012 LEE
dc.identifier.citationLee, Chang-Chun. "Interactions of Amyloid-Forming Peptides with Lipid Bilayer Membranes." (2012) Diss., Rice University. <a href="https://hdl.handle.net/1911/70308">https://hdl.handle.net/1911/70308</a>.
dc.identifier.digitalLeeCen_US
dc.identifier.urihttps://hdl.handle.net/1911/70308
dc.language.isoeng
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.
dc.subjectPure sciences
dc.subjectBiological sciences
dc.subjectAmyloid-forming peptides
dc.subjectLipid bilayer membranes
dc.subjectNeutron in-plane scattering
dc.subjectAntimicrobial peptides
dc.subjectOriented circular dichroism
dc.subjectBiochemistry
dc.subjectBiophysics
dc.titleInteractions of Amyloid-Forming Peptides with Lipid Bilayer Membranes
dc.typeThesis
dc.type.materialText
thesis.degree.departmentPhysics
thesis.degree.disciplineNatural Sciences
thesis.degree.grantorRice University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
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