eprintid: 10968
rev_number: 19
userid: 540
dir: disk0/00/01/09/68
datestamp: 2012-06-01 18:30:39
lastmod: 2016-11-15 13:55:59
status_changed: 2012-06-01 18:30:39
type: thesis_degree
metadata_visibility: show
contact_email: lem64@pitt.edu
item_issues_count: 0
eprint_status: archive
creators_name: Marbella, Lauren E.
creators_email: lem64@pitt.edu
creators_id: LEM64
title: INVESTIGATING MITOCHONDRIA PENETRATING PEPTIDES WITH SOLID STATE NMR USING MODEL MEMBRANES
ispublished: unpub
divisions: sch_as_chemistry
full_text_status: public
keywords: penetrating peptides, mitochondria, NMR spectroscopy, translocation mechanism, lipid-peptide interaction
abstract: Penetrating peptides are unique peptides that can translocate across membranes in a non-lytic fashion. A new class of penetrating peptides that can target the mitochondria with high specificity have been developed. Targeting the mitochondria is therapeutically valuable, given the organelle’s role in energy production and apoptosis. The peptide we studied is sufficiently cationic and hydrophobic and is hypothesized to reach the mitochondrial matrix. However, the mechanism of translocation remains unknown. In our work, we use solid state NMR to gain insight into the mechanism of translocation of this mitochondria-penetrating peptide. We use static 31P NMR the membrane morphology and peptide-induced structure changes. The paramagnetic relaxation effect examined through 13C MAS NMR was used for insertion depth determination and to distinguish bilayer sidedness. We found that the peptide does not disrupt the lamellarity. Also, at low peptide concentrations the peptide binds to the outer leaflet and at high concentrations crosses the hydrophobic bilayer core and is distributed in both leaflets. Our findings support the electroporation model of translocation, but we did not observe complete translocation of the peptide.  We examine the energy associated with crossing the inner mitochondrial membrane to determine the feasibility of the peptide reaching the mitochondrial matrix.
date: 2012-06-01
date_type: published
pages: 59
institution: University of Pittsburgh
refereed: TRUE
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_type: committee_chair
etdcommittee_name: Saxena, Sunil K.
etdcommittee_name: Amemiya, Shigeru
etdcommittee_name: Spence, Megan M.
etdcommittee_email: sksaxena@pitt.edu
etdcommittee_email: amemiya@pitt.edu
etdcommittee_email: mspence@pitt.edu
etdcommittee_id: SKSAXENA
etdcommittee_id: AMEMIYA
etdcommittee_id: MSPENCE
etd_defense_date: 2011-06-09
etd_approval_date: 2012-06-01
etd_submission_date: 2012-02-08
etd_release_date: 2012-06-01
etd_access_restriction: immediate
etd_patent_pending: FALSE
assigned_doi: doi:10.5195/pitt.etd.2012.10968
thesis_type: thesis
degree: MS
citation:   Marbella, Lauren E.  (2012) INVESTIGATING MITOCHONDRIA PENETRATING PEPTIDES WITH SOLID STATE NMR USING MODEL MEMBRANES.  Master's Thesis, University of Pittsburgh.    (Unpublished)  
document_url: http://d-scholarship-dev.library.pitt.edu/10968/7/Lauren_Marbella_Thesis.pdf