膜蛋白组织的脂质控制-猫眼课题宝

膜蛋白组织的脂质控制

批准号：

7172298

负责人：

RICHARD MENDELSOHN

金额：

$28.75万

依托单位：

RUTGERS THE STATE UNIV OF NJ NEWARK

依托单位国家：

美国

项目类别：

财政年份：

1996

资助国家：

美国

项目状态：

已结题

起止时间：

1996-07-01 至 2009-01-31

来源：

https://reporter.nih.gov/project-details/7172298

关键词：

3-Dimensional Air Area Attenuated Binding Biological Biological Models Biological Process Ceramides Characteristics Charge Class Complement Complex Condition Disease Drug Delivery Systems Elements Enhancers Event Film Funding Goals Grant Host Defense Image Imaging technology In Situ Laboratories Ligands Lipids Lung Maps Measures Membrane Membrane Lipids Membrane Proteins Methods Microscopic Microscopy Modeling Modification Molecular Molecular Conformation Molecular Structure Monitor Newborn Respiratory Distress Syndrome Pathway interactions Penetration Peptides Permeability Preparation Property Protein Conformation Proteins Pulmonary Surfactant-Associated Protein B Pulmonary Surfactants Research Personnel Role Secondary Protein Structure Skin Spatial Distribution Spectrum Analysis Stratum corneum Structure Surface System Technology Testing Therapeutic Agents Thermodynamics Thinking Variant Vesicle Water absorption analog aqueous base in vivo infrared spectroscopy interest interfacial monolayer novel peptide analog physical state pressure programs research study surfactant synthetic peptide three dimensional structure tubular myelin

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DESCRIPTION (provided by applicant): A long-term goal of this laboratory has been to determine the role of lipid/protein interaction in the function of pulmonary surfactant. A more recent interest has been to determine the roles of the various lipid species in the structure of the barrier to permeability in skin. Two specific aims, each with a physical and biological/biomedical component related to these goals, will be pursued: Aim 1: Physical: To extend infrared reflection-absorption spectroscopy (IRRAS), for determination of elements of the 3-dimensional structure of lipid monolayers in situ at the A/W interface. Biological: To test the hypothesis that the hydrophobic surfactant proteins SP-B and C facilitate the formation/stabilization of multilayers that act as reservoirs for surface-active material during lung compression-expansion cycles. To complement IRRAS, Brewster angle microscopy, pressure-area isotherms, and pulsating bubble surfactometry will be used to characterize these films. Equivalent experiments with synthetic peptides will help define structural characteristics needed for peptides to be useful therapeutic agents for diseases such as respiratory distress syndrome. We will also evaluate the interactions of lung surfactant SP-A analogues with lipids and other ligands to determine its role in tubular myelin formation and in host defense. Aim 2: Physical: To apply 3 novel vibrational microscopic imaging technologies (IR microscopic imaging, confocal Raman microscopy, and attenuated total reflectance imaging) to acquire spatially resolved molecular structure information at distance scales from 1.5 mm to 4 mm. These will be used to study lipid domain formation in model systems for the skin barrier. The experiment aims to understand the role of the various ceramide species in barrier function. Biological: To use these methods to study the 3-D spatial distribution of the molecular constituents of skin as well as the permeation pathways of penetration enhancers and drug delivery vehicles. Finally, the sensitivity of vibrational spectra to molecular structure will be used to map the effects of penetration enhancers on lipid conformation and protein secondary structure.

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