Monitoring the Effects of Synthetic Lung Surfactant Peptides on Lipid Bilayer Dynamics and Fluidity

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Material Information

Title:
Monitoring the Effects of Synthetic Lung Surfactant Peptides on Lipid Bilayer Dynamics and Fluidity
Physical Description:
1 online resource (146 p.)
Language:
english
Creator:
Braide, Otonye H
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Chemistry
Committee Chair:
FANUCCI,GAIL E
Committee Co-Chair:
TALHAM,DANIEL R
Committee Members:
OMENETTO,NICOLO
SMITH,BEN W
LONG,JOANNA R

Subjects

Subjects / Keywords:
biomembrane -- hypophase -- kl4 -- lipids -- liposomes -- lung -- phospholipids -- pulmonary -- respiratory -- sp-b -- surfactant
Chemistry -- Dissertations, Academic -- UF
Genre:
Chemistry thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
Premature infants with underdeveloped lungs typically develop respiratory distress syndrome (RDS) because their lungs lack the surfactant lining crucial for oxygen absorption or have genetically failed to produce critical components of lung surfactant (LS) needed for proper function. The LS is a complex mixture of lipids and proteins known to provide a protective barrier against inhaled pathogens, lower alveolar surface tension and promote oxygen exchange. The functional significance of LS is clear; however, a detailed mechanistic understanding of how lipids are trafficked to and from the air-fluid interface for oxygen absorption remains unknown. Though the bulk of LS is made up of lipids (~90%), it is non-functional without the presence of surfactant proteins (SP-A, B, C, and D), especially SP-B, which is known to reduce surface tension and closely associates with lipids in the bulk phase of liquid below alveoli surface film (hypophase). As SP-B is highly hydrophobic and structurally complex, challenges in synthesis and expression of a functionally active recombinant have led to increased efforts to use synthetic alternatives in developing novel therapeutics for RDS treatment, and to elucidate the mechanism of function. Within the scope of this dissertation, we use alternatives such as KL4, a mimetic of SP-B, and SP-B59-80; which have been shown to retain the fundamental properties necessary for LS function when in the presence of major phospholipid constituents, as model systems to further our understanding of fundamental membrane-protein interactions and of specific LS components function. Fluorescence and electron paramagnetic resonance techniques were used to investigate the effects of the synthetic peptides on lipid dynamics, fluidity, and to model peptide depth profiles in lipid bilayers. The results from these experiments suggested a deeper penetration of the peptide into lipid systems that are rich in the main lipid found at the air-fluid interface monolayer; and also showed induction of curvature strains in the bilayer, both of which correlate with the hypothesized mechanism of lipid flipping to the air-fluid interface. Circular dichroism was used to evaluate pH effects on peptide conformation, which highlighted the importance of using biologically relevant conditions to accurately model the molecular biophysics of LS.
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Otonye H Braide.
Thesis:
Thesis (Ph.D.)--University of Florida, 2014.
Local:
Adviser: FANUCCI,GAIL E.
Local:
Co-adviser: TALHAM,DANIEL R.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2014-11-30

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2014
System ID:
UFE0046708:00001