Measurement of Cellular Viscosity and Mitochondrial Dynamics using Ultrasensitive Imaging Methods
Abstract
We propose to apply ultrasensitive optical detection techniques recently developed by Dr. Warwick Bowen’s research group at University of Queensland to establish non-destructive, real-time, single-cell measurement platforms to measure two important biophysical attributes of the cell, viscosity and mitochondria-dependent bioactivity, both of which are critical for cell activity and fate determination. The variation in cytoplasmic viscosity might be of importance in the course of differentiation or homeostasis. It is increasingly recognized that mechanical signals from cell microenvironment play important roles in regulating various cell behaviors. Therefore, in the first part of this project, we plan to study how extracellular matrix mechanical properties regulate cell viscosity, and how cytoplasmic viscosity regulates biochemical reactions. We will visit Dr. Bowen’s laboratory and apply the ultrafast viscosity measurement technology developed by Dr. Bowen and his research team, to measure viscosity, and correlate the obtained values with the substrate stiffness and viscoelasticity, the rate of important biological processes including lysosome transportation and microtubule dynamics. In the second part of the project, we will explore whether the quantum-limit light scattering measurement, also developed by Dr. Bowen’s group, can be used to probe the health state of cells, and evaluate the relation between the health state readout and the biophysics of mitochondria. Not only mitochondria synthesize ATP to meet the fluctuating energetic demands of the cell as it undergoes different cellular processes, they also serve as the regulator of stress responses. We hypothesize that the highly dynamic processes of mitochondria likely give rise to the signature indicating a certain health state of the cell. The different health states can be achieved by irradiating cells with different doses of ultraviolet light. Dr. Bowen’s team will build the specialized microscope, coined bioactivity frequency mapping (BFM) microscope, which implements the quantum-limited light scattering technique, in our laboratory at Johns Hopkins University for the bioactivity measurement. By measuring bioactivity using BFM and mitochondrial dynamics (i.e. mobility and metabolic rate) using fluorescence microscopy, we aim to establish the quantitative relation between mitochondrial dynamics and cellular health states.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 07, 2023
- Source ID
- FA95502110284
Entities
People
- Yun Chen
Organizations
- Air Force Office of Scientific Research
- Johns Hopkins University
- United States Air Force