Effect of Charge on Adsorption of Pulmonary Surfactant

描述(申请人提供)：复杂的肺表面活性物质(PS)混合物的主要成分包括中性、两性和阴离子脂类，以及阳离子蛋白质。功能性PS必须在几秒钟内在新形成的空气/水界面上吸附，并在呼吸过程中机械地稳定肺。肺泡内PS供应不足可导致早产儿出现呼吸窘迫综合征或成人出现急性呼吸窘迫综合征。通过表面活性物质替代疗法进行治疗是昂贵的。关于PS如何工作的基本机制还没有被很好地理解。静电相互作用被认为在初始吸附过程中发挥了作用。这一建议的第一个目的是检验这样一种假设，即PS电荷的有效屏蔽有助于表面活性剂接近空气/水界面，从而提高吸附速度。第二个目的是测试蛋白质的存在是否通过充当其自身阳离子电荷和PL阴离子电荷之间的静电系绳或桥梁来提高吸附速度。这些假设将通过使用各种表面活性剂和亚相组成的表面张力计和显微镜进行实验验证。这个项目的成功完成将大大有助于从根本上理解PS的吸附机理。

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.