Effect of Charge on Adsorption of Pulmonary Surfactant

描述（由申请人提供）：复合肺表面活性剂（PS）混合物的关键成分包括中性、两性离子和阴离子脂质，以及阳离子蛋白。功能性PS必须在几秒钟内吸附在新形成的空气/水界面上，并在呼吸过程中机械地稳定肺部。肺泡中缺乏足够的PS供应可导致早产儿呼吸窘迫综合征或成人急性呼吸窘迫综合征。通过表面活性剂替代疗法治疗是昂贵的。详细说明PS如何工作的基本机制尚未得到很好的理解。静电相互作用被认为在初始吸附过程中起作用。本提案的第一个目的是验证这样一个假设，即有效筛选PS电荷有助于表面活性剂接近空气/水界面，从而提高吸附速率。第二个目的是测试蛋白质的存在是否通过在其自身的阳离子电荷和PL的阴离子电荷之间充当静电系绳或桥梁来提高吸附速率。这些假设将通过使用各种表面活性剂和亚相成分的表面张力测定法和显微镜进行实验测试。该项目的成功完成将对PS吸附机理的基本认识作出重大贡献。

DESCRIPTION (provided by applicant): The key components of the complex pulmonary surfactant (PS) mixture include neutral, zwitterionic, and anionic lipids, as well as cationic proteins. Functional PS must adsorb within seconds at a newly formed air/water interface and stabilize the lungs mechanically during the breathing process. Lack of an adequate supply of PS in the alveoli can lead to Respiratory Distress Syndrome in premature infants or Acute Respiratory Distress Syndrome in adults. Treatment via surfactant replacement therapies is expensive. The fundamental mechanisms detailing how PS works are not yet well understood. Electrostatic interactions are thought to play a role in the initial adsorption process. The first aim of this proposal is to test the hypothesis that the effective screening of PS charge facilitates the close approach of the surfactant to the air/water interface, thereby enhancing the rate of adsorption. The second aim is to test whether the presence of protein enhances the adsorption rate by acting as an electrostatic tether or bridge between its own cationic charge and the anionic charge of the PL. These hypotheses will be experimentally tested with surface tensiometry and microscopy using a variety of surfactant and subphase compositions. Successful completion of this project should significantly contribute to the fundamental understanding of the PS adsorption mechanism.