Interactions of Amyloid-Forming Peptides with Lipid Bilayer Membranes

Simple item page
dc.contributor.advisorHuang, Huey W.en_US
dc.creatorLee, Chang-Chunen_US
dc.date.accessioned2013-03-08T00:35:29Zen_US
dc.date.available2013-03-08T00:35:29Zen_US
dc.date.issued2012en_US
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.en_US
dc.format.extent153 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS PHYS. 2012 LEEen_US
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>.en_US
dc.identifier.digitalLeeCen_US
dc.identifier.urihttps://hdl.handle.net/1911/70308en_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.subjectPure sciencesen_US
dc.subjectBiological sciencesen_US
dc.subjectAmyloid-forming peptidesen_US
dc.subjectLipid bilayer membranesen_US
dc.subjectNeutron in-plane scatteringen_US
dc.subjectAntimicrobial peptidesen_US
dc.subjectOriented circular dichroismen_US
dc.subjectBiochemistryen_US
dc.subjectBiophysicsen_US
dc.titleInteractions of Amyloid-Forming Peptides with Lipid Bilayer Membranesen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentPhysicsen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
LeeC.pdf
Size:
6.92 MB
Format:
Adobe Portable Document Format
Download
Collections
Rice University Theses and Dissertations