Nonlinear Light Scattering Spectroscopy and Microscopy of Molecular Interactions at Biological Surfaces

生物表面分子相互作用的非线性光散射光谱和显微镜

• 批准号: 1465096
• 负责人: Hai-Lung Dai
• 金额: $ 51.03万
• 依托单位: Temple University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1465096&HistoricalAwards=false
• 关键词: Nonlinear; Light; Scattering; Spectroscopy; Microscopy

With this award, the Chemical Structure, Dynamics and Mechanisms (CSDM-A) Program of the Division of Chemistry is funding Professor Hai-Lung Dai of Temple University to use a newly developed, laser-based technique to measure how drug-like molecules adsorb and transport through biological cell membranes. The knowledge gained here is important for the advancement of fundamental research in life sciences. It is also highly beneficial to chemical biology and pharmaceutical sciences research by providing a method to determine the rates of drug transport through cell membranes. Students participating in this research are prepared with a wide range of expertise in interdisciplinary areas involving biology, chemistry, medicine and physics, and as such, for careers in fundamental biomedically related research in academia and industry. Professor Dai's laboratory will continue to provide research opportunities for undergraduate students and high/middle school science teachers.In the proposed studies, nonlinear light scattering methods with their intrinsic surface sensitivity, and time-, frequency-, and spatial-resolution, are used to provide a molecular level description of how molecules interact with biological surfaces. This newly developed method will be applied in several areas including determining: 1) how molecular and membrane structures affect molecular transport though cell membranes; 2) how membrane permeabilizers and cell-penetrating peptides work; and 3) what are the underlying energetic factors and forces that are behind the Hofmeister series. In addition, second harmonic microscopy for time-resolved imaging of molecular transport through membranes and molecular intake into cells is to be developed. This project aims to provide enhanced understanding of a range of problems related to life processes. For example, though much is known about how atomic cations transport through cell membranes, little is known about how molecular or membrane structure affects transport of small or medium size molecules. Moreover, the mechanism of action of membrane permeabilizers is unknown. In addition, the driving forces behind the century old Hofmeister effect are poorly understood. The proposed research seeks to make advances that impact a range of scientific areas including nonlinear optics, colloidal science, protein function, and cell membrane transport mechanism.

凭借该奖项，化学系的化学结构、动力学和机制 (CSDM-A) 项目正在资助天普大学的 Hai-Lung Dai 教授使用一种新开发的基于激光的技术来测量类药物分子如何通过生物细胞膜吸附和运输。在这里获得的知识对于生命科学研究的进步非常重要。 通过提供一种确定药物通过细胞膜转运速率的方法，它对化学生物学和药物科学研究也非常有益。参与这项研究的学生在涉及生物学、化学、医学和物理学的跨学科领域具备广泛的专业知识，因此可以为学术界和工业界从事基础生物医学相关研究的职业做好准备。戴教授的实验室将继续为本科生和高中/中学科学教师提供研究机会。在拟议的研究中，非线性光散射方法以其固有的表面敏感性以及时间、频率和空间分辨率，用于提供分子如何与生物表面相互作用的分子水平描述。这种新开发的方法将应用于多个领域，包括确定：1）分子和膜结构如何影响分子通过细胞膜的运输； 2) 膜透化剂和细胞穿透肽如何发挥作用； 3）霍夫迈斯特级数背后的潜在能量因素和力量是什么。 此外，还将开发用于对通过膜的分子运输和细胞内的分子摄入进行时间分辨成像的二次谐波显微镜。该项目旨在加深对与生命过程相关的一系列问题的理解。例如，尽管人们对原子阳离子如何通过细胞膜运输了解甚多，但对分子或膜结构如何影响小或中等尺寸分子的运输知之甚少。此外，膜透化剂的作用机制尚不清楚。此外，人们对百年霍夫迈斯特效应背后的驱动力知之甚少。 拟议的研究旨在取得影响一系列科学领域的进展，包括非线性光学、胶体科学、蛋白质功能和细胞膜运输机制。