NEAR FIELD SCANNING OPTICAL MICROSCOPY STUDY OF THE MEC

MEC 的近场扫描光学显微镜研究

• 批准号: 6343495
• 负责人: BRET N FLANDERS
• 金额: $ 3.38万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-20 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6343495
• 关键词: atomic force microscopy; bioimaging /biomedical imaging; confocal scanning microscopy; molecular film; nanotechnology; palmitates; pathologic process; pulmonary surfactants; respiratory distress syndrome of newborn

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.

肺表面活性物质（LS）单层的塌陷导致呼吸窘迫综合征（RDS）。 拟议的研究的目的是使用近场扫描光学显微镜（NSOM）的高分辨率技术，以开发的域分区和塌陷特性的多组分膜，非常类似于天然肺表面活性剂（LS）的理解，以发现创新的治疗RDS。 迄今为止，已对仅由天然LS中存在的几种脂质和蛋白质组分中的少数组成的单层进行了类似于人肺表面活性剂的单层的体外研究。 因此，这些研究反映自然肺环境中单层细胞塌陷的程度尚不清楚。 因此，该项目的主要目标是系统地了解与天然LS非常相似的多组分薄膜的塌陷。 为此，该项目分为四个阶段，涉及1）单一脂质单层2）单一脂质/蛋白质单层3）混合脂质单层4）混合脂质/蛋白质单层的NSOM和AFM研究。 因此，可以鉴定和表征不同脂质组分之间的重要成对和协同效应。 此外，NSOM的5-8埃单位垂直和小于100 nm的横向空间分辨率将允许单层以前所未有的细节成像。 精细的垂直分辨率使得研究垂直特征的早期生长（在名义上的二维单层上）成为可能，这些特征预计会在单层崩溃开始时出现。 因此，可以用亚纳米细节来研究RDS的根本生理原因塌陷。 因此，本研究项目的主要目标是产生一个现实的和详细的了解LS单层塌陷过程，然后使用这种理解作为指导设计新的治疗RDS。