Understanding the Mission Versatility of Membrane Proteins and Cells by All-Scale Nanoscopic Imaging
Abstract
Biological functions emerge at the level of single biomolecules and develop further complexity from their organization and communications at length scales all the way up to the cell and tissue regime. In an action potential, for instance, charge- and stimulus-selectivity are derived from the structure and fluctuations of the membranes and membrane proteins at play, whereas larger scale bioelectrical signaling depends on their cooperativity in space and time across a whole synapse or neuron. Similar scale-bridging behavior is present in enzymatic reaction networks, immunological response, and more. This proposal aims to develop Aurora , an experimental approach to film these structures, interrelationships, and dynamics in preserved liquid environment with nanometer resolution at every scale. The core of Aurora is liquid-phase transmission electron microscopy (TEM), on which the PI pioneered efforts in previous funding cycles to transform it into a powerful new lens into nanoscale biophysics at the unprecedented nanometer and millisecond resolutions. Liquid-phase TEM bridges the gap between optical microscopy and cryogenic electron microscopy by preserving biomolecular specimens in liquids. Aurora will further draw from recent advancements in liquid chamber design, high-throughput imaging and analysis supported by machine learning, in situ stimulation technology, serial sectioning, and electron tomography and diffraction. The proposed work will explore new directions in active imaging to understand out-of-equilibrium behavior of enzymes and ion channels stimulated by temperature, electric fields, and chemical reactions and functional imaging to understand the dynamic interface between a pillar of the immune system (T cells) and antigen-presenting cells and cell mimetics.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 07, 2024
- Source ID
- FA95502310609
Entities
People
- Qian Chen
Organizations
- Air Force Office of Scientific Research
- United States Air Force
- University of Illinois Urbana–Champaign