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

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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.