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Study of Structure and Dynamics of Monolayers Containing STUDY OF STRUCTURE AND DYNAMICS OF MONOLAYERS CONTAINING PROTEINS AND LIPIDS AT THE AIR-WATER INTERFACE USING TWO DIMENSIONAL INFRARED SPECTROSCOPY METHODS by SARATCHANDRA SHANMUKH (Under the Direction of Richard A. Dluhy) ABSTRACT Chapters 3 – 8 of this dissertation are composed of individual manuscripts which have either been published or submitted to scholarly journals. In Chapter 3, 2D IR correlation analyses are performed on IRRAS spectra of surfactant proteins B and C containing lipid monolayers at the air-water interface. Based on the correlation plots, it was concluded that the secondary structures of SP-B and SP-C are heterogenous and change with increase in surface pressure. Chapter 4 describes an investigation using infrared spectroscopy into the change in the secondary structure of deacylated SP-C with pH. In Chapter 5, a new model-based 2D IR method is introduced and described using simulated spectral models. This method, kν correlation, makes use of a set of simulated exponential curves that are mathematically cross-correlated against a set of experimental curves and the resulting correlation plot between spectral frequency and rate constant reveals temporal relationships in terms of a numerical parameter. In Chapter 6, the kν correlation method is used to study the interaction between a phospholipid (DPPA) monolayer and the antibiotic Tetracycline by collecting PM-IRRAS spectra at the air-water interface. A synthetic peptide, mSP-B1-25, is characterized using PM-IRRAS at the air-water interface and kν correlation to determine if it can be used as an effective replacement for the native SP-B protein in lung surfactant. This study, presented in Chapter 7, revealed the changes in secondary structure of the peptide present in different concentrations in a lipid matrix of deuterated DPPC and DOPG on subphases containing sodium and calcium ions. In Chapter 8, Ag nanorod substrates, that are prepared by vapor deposition on the substrate at an oblique angle, are characterized for their SERS activity. Nanorod samples of different lengths were characterized at 785nm using 1,2-trans(bi-pyridyl)-ethene as a probe molecule. Surface Enhancement factors of 108 were observed and the enhancement factor was found to increase with increase in the length of the nanorods. INDEX WORDS: Fourier Transform Infrared Spectroscopy (FT-IR), Infrared Reflection- Absorption Spectroscopy (IRRAS), Two Dimensional Infrared Correlation Analysis (2D-IR), Air-water Interface, Polarization Modulation IRRAS, Surface Enhanced Raman Scattering, DPPC, Pulmonary Surfactant, SP-B, SP-C, Nanorods, GLAD STUDY OF STRUCTURE AND DYNAMICS OF MONOLAYERS CONTAINING PROTEINS AND LIPIDS AT THE AIR-WATER INTERFACE USING TWO DIMENSIONAL INFRARED SPECTROSCOPY METHODS by SARATCHANDRA SHANMUKH B.Sc., University of Madras, India 1998 M.Sc., Indian Institute of Technology Madras, India, 2000 A Dissertation Submitted to the Graduate Faculty of The University of Georgia in Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY ATHENS, GEORGIA 2005 © 2005 Saratchandra Shanmukh All Rights Reserved STUDY OF STRUCTURE AND DYNAMICS OF MONOLAYERS CONTAINING PROTEINS AND LIPIDS AT THE AIR-WATER INTERFACE USING TWO DIMENSIONAL INFRARED SPECTROSCOPY METHODS by SARATCHANDRA SHANMUKH Major Professor: Richard A. Dluhy Committee: Jonathan Amster Geoffrey Smith Electronic Version Approved: Maureen Grasso Dean of the Graduate School The University Of Georgia May 2005 ACKNOWLEDGEMENTS I would first like to thank my wife, Kala, for all her love, support and help without which this work would not be possible. I would also like to thank my parents, brother and grandparents for their love and encouragement. I wish to express my deepest gratitude to my research advisor, Richard A. Dluhy, for his mentoring, support and encouragement during the course of my research. Acknowledgement is also due to my committee members, Jonathan Amster, Geoffrey Smith and Lucia Babcock for reviewing my dissertation and guidance throughout the duration of my Ph.D. I would like to thank the past and current members of the Dluhy research group for all their guidance, ideas and support throughout my Ph.D. Finally, I would like thank the University Of Georgia and the Government of the United States of America for giving me the opportunity to visit and experience this amazing country. iv TABLE OF CONTENTS Page ACKNOWLEDGEMENTS........................................................................................................... iv CHAPTER 1 INTRODUCTION ..........................................................................................................1 2 LITERATURE REVIEW ...............................................................................................5 3 EFFECT OF HYDROPHOBIC SURFACTANT PROTEINS SP-B AND SP-C ON PHOSPHOLIPID MONOLAYERS: PROTEIN STRUCTURE STUDIED USING 2D IR AND βν CORRELATION ANALYSIS...............................................92 4 DE-ACYLATED PULMONARY SURFACTANT PROTEIN SP-C TRANSFORMS FROM α-HELICAL TO AMYLOID FIBRIL STRUCTURE VIA A pH DEPENDENT MECHANIMS: AN IR STRUCTURAL INVESTIGATION......................................................................................................153 5 kν CORRELATION ANALYSIS: A QUANTITATIVE TWO-DIMENSIONAL IR METHOD FOR ANALYSIS OF RATE PROCESSES WITH EXPONENTIAL FUNCTIONS ..............................................................................................................209 6 2D IR ANALYSES OF RATE PROCESSES IN LIPID-ANTIBIOTIC MONOMOLECULAR FILMS..................................................................................260 7 STRUCTURE AND PROPERTIES OF PHOSPHOLIPID-PEPTIDE MONOLAYERS CONTAINING MONOMERIC SP-B1-25: PEPTIDE CONFORMATION BY INFRARED SPECTROSCOPY .........................................303 v 8 RANDOMLY ALIGNED SILVER NANOROD ARRAYS PRODUCE HIGH SENSITIVITY SERS SUBSTRATES ............................................................352 9 CONCLUSIONS.........................................................................................................369 vi CHAPTER 1 INTRODUCTION Biomembranes found in nature have complex structures and multiple components that continuously interact with each other and with other components present in the immediate environment. Pulmonary surfactant is the mixture of lipids and specific proteins produced by type II pneumocytes in the alveolar epithelium that lines the air-alveolar fluid interface of the lung and is needed to reduce alveolar surface tension to near zero at low lung volumes and prevent end-expiratory collapse. Deficiency of one or more components of this mixture has been shown to cause Respiratory Distress Syndrome (RDS) in premature infants, and has also been implicated in the Acute Respiratory Distress Syndrome (ARDS) that can result from lung injury due to a variety of causes. An insoluble monolayer film of amphipathic molecules spread at the air-water interface is commonly known to as a Langmuir monolayer. Since Langmuir monolayers are also 2-D dynamically compressed films at the A/W interface, they can be used as a model experimental system to study the structure, dynamics and the mechanism by which pulmonary surfactant lowers surface tension at the alveolar air-water interface. Several methods have been applied to the study of the structure of biomembranes observed in nature. The work presented in this dissertation utilizes modern experimental techniques such as Polarization Modulation Infrared Absorption Spectroscopy at the air-water interface (PM- IRRAS) and Two-Dimensional Infrared Correlation spectroscopy (2D IR) to study the structure, 1 nature of interaction between different components and their dynamic behavior. Infrared external reflection spectroscopy, also referred to as IRRAS, has been used to study monomolecular thin films on metal surfaces for several years. The use of external reflection FT-IR spectroscopy to study monomolecular films directly at the air-water interface was originally developed in the mid 1980s and this represented a major step in the application of IRRAS to the study of biologically relevant membranes and molecules in an environment closest to what is found in nature. IRRAS at the air-water interface is hindered by interference due to isotropic water vapor absorption and baseline dispersion effects due to the water substrate. In order to overcome these inherent limitations, polarization modulation spectroscopy has been applied to monomolecular films at the air-water interface. Polarization Modulation Infrared Reflectance Spectroscopy (PM - IRRAS) involves a fast modulation of the polarization of the incidence electric field between parallel and perpendicular linear polarization states. After electronic filtering and demodulation of the signal using a lock-in amplifier, the differential reflectivity spectrum is then computed. The Polarization Modulation Reflectance spectrum is insensitive to isotropic absorptions and reflects the difference between the parallel and perpendicular polarizations. Two-dimensional infrared correlation spectroscopy (2D IR) is a modern analytical technique that is increasingly being used in the interpretation of complex spectra, which generally have broad, multiply overlapped spectral features. Besides functioning as a spectral resolution enhancement method similar to curve fitting or deconvolution, 2D IR possesses an additional advantage, in that it is capable of discerning temporal relationships between intensity variations within the set of spectra. βν Correlation
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