NEAR FIELD SCANNING OPTICAL MICROSCOPY STUDY OF THE MEC

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Collapse of the lung surfactant (LS) monolayer causes respiratory distress syndrome (RDS). The proposed research is aimed at using the high resolution technique of near-field scanning optical microscopy (NSOM) to develop an understanding of the domain partitioning and collapse properties of multi-component films that closely resemble natural lung surfactant (LS) in order to discover innovative treatments for RDS. To date, in vitro studies of monolayers resembling the human lung surfactant have been performed on monolayers that are composed of only a few of the several lipid and protein components that are present in natural LS. Hence, the degree to which these studies reflect monolayer collapse in the natural pulmonary environment is not known. Therefore, a primary goal of this project is to systematically develop an understanding of collapse in multi-component films that closely resemble natural LS. To this end, the project is structured in four stages involving NSOM and AFM study of 1) single lipid monolayers 2) single lipid/protein monolayers 3) mixed lipid monolayers 4) mixed lipid/protein monolayers. Hence, identification and characterization of important pair-wise and synergistic effects between different lipid components may be made. Furthermore, the 5-8 Angstrom units vertical and less than 100nm lateral spatial resolution of NSOM will allow the monolayers to be imaged with unprecedented detail. The exquisite vertical resolution makes possible the study of early growth of vertical features (on the nominally two-dimensional monolayers) that are expected to appear as monolayer collapse begins to occur. Hence, collapse, the root physiological cause of RDS, may be studied with sub-nanometer detail. Thus, the primary goal of this research project is to generate a realistic and detailed understanding of the LS monolayer collapse process and then to use this understanding as guidance in designing novel treatments for RDS.