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: 6013032
• 负责人: BRET N FLANDERS
• 金额: $ 3.03万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-20 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6013032
• 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）单层塌陷引起呼吸窘迫综合征（RDS）。该研究旨在利用高分辨率的近场扫描光学显微镜（NSOM）技术来了解与天然肺表面活性剂（LS）非常相似的多组分薄膜的畴划分和坍缩特性，从而发现治疗RDS的创新方法。迄今为止，对类似人肺表面活性剂的单分子膜进行的体外研究仅由天然LS中存在的几种脂质和蛋白质成分中的几种组成。因此，这些研究在多大程度上反映了自然肺环境中的单层塌陷尚不清楚。因此，这个项目的主要目标是系统地发展对多组分薄膜的崩塌的理解，这些薄膜与自然LS非常相似。为此，该项目分为四个阶段，包括NSOM和AFM研究：1)单个脂质单层；2)单个脂质/蛋白单层；3)混合脂质单层；4)混合脂质/蛋白单层。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埃的垂直空间分辨率和小于100nm的横向空间分辨率将使单层成像具有前所未有的细节。精致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坍塌开始发生时出现。因此，塌陷作为RDS的根本生理原因，可以在亚纳米尺度上进行研究。因此，本研究项目的主要目标是对LS单层塌陷过程产生现实和详细的理解，然后将这种理解作为设计RDS新治疗方法的指导。