OPT-PDE Analysis and FRET Imaging of Constitutive Connections between Physics and Chemistry in Live Cells

University Of California-San Diego, La Jolla CA

Investigators

Abstract

Understanding molecular transport and interaction within single live cells is crucial for advancing life sciences and medicine. This project integrates mathematics with live-cell imaging to study diffusion tensor maps and the relationship between molecular transport and interaction in live cells. For this purpose, mathematical theory and computational algorithms will be developed for applications in image-based quantitative biology. This project integrates research with education and will provide research training opportunities for students. An annual summer workshop, featuring computational mathematics, live cell imaging, and quantitative biology, will be organized for graduate and undergraduate students. Members of underrepresented groups will be encouraged to participate in both the research training and workshop activities. Outreach activities will bring the project's laboratory research results to high school students. The research goal of this project is to establish governing equations connecting physics and chemistry in live cells. Molecular diffusion and transport are fundamental processes in biology, biochemistry, and physics. However, the construction of subcellular diffusion maps in living cells based on imaging data remains a challenge. This project will develop an optimization model problem with partial differential equation constraints (OPT-PDE) to compute the diffusion map of intracellular molecules with high spatiotemporal resolution in live cells. Meanwhile, this project will apply fluorescence resonant energy transfer (FRET)-based biosensors to visualize subcellular molecular activities. The correlative FRET imaging microscopy (CFIM) technology will then be employed to evaluate the connection between the subcellular diffusion and the molecular activity imaged by FRET in live cells. Specifically, the protein tyrosine kinases Src and FAK will be selected as examples to demonstrate this connection. Therefore, the results of this project will reveal the spatiotemporal connection between biochemical activities and biophysical properties of desired molecules in live cells.