EAGER: Live Cell Imaging using Low Dose 4DSTEM

University Of Texas At Austin, Austin TX

Investigators

Abstract

Modern biological research is driven by a need to observe living cells and structures at ever-finer levels of detail. Most of the live-cell cell imaging work relies on visible or fluorescent light imaging because higher resolutions methods, like transmission electron microscopy (TEM) use higher energies and sample preparation methods that are lethal to cells. The current limitation of beam induced damage to live cells is thus preventing this field from moving to the next phase of nanoscale live biological imaging. Researcher supported by this award will overcome this challenge by developing new, non-lethal TEM imaging methods to enable live cell imaging in unparalleled detail. Knowledge gained form these studies will be integrated into the ‘Practical Electron Microscopy’ course at UT Austin. In addition, undergraduate research projects will be offered at UT Austin as part of the EUREKA program and participation from underrepresented groups will be actively encouraged. The studies will also be featured at public science activities like the annual ‘Girl Day’ at UT Austin, where over 8,000 elementary and middle school students visit UT Austin and have hands-on experience with science and engineering; and at the annual ‘Black Excellence in STEM’ event at UT Austin during Black History Month. The researchers will also participate in the annual ‘Explore UT’, the open day where thousands of out-of-town residents visit campus to participate in high-touch, interactive, hands-on programs. Nanoscale imaging of live cells and biological processes will be undertaken using advanced low-dose 4D scanning transmission electron microscopy (4D-STEM). High contrast imaging to observe live cells with non-lethal electron doses will be done using a liquid cell in situ holder and highly sensitive ultrafast pixelated direct electron detectors. Studies will start with the observation of cell membranes interacting with nanoscale objects such as exosomes and virus to provide new dynamical insights of live cells in various biological processes. Observing live cells with nanoscale resolution opens a new field of real time dynamics in biology at length scales that are current inaccessible. The imaging methods, informatics and experimental procedures developed through this award will be used in studies for a wide range of biological systems, including intercellular communication, virus:cell membrane interactions, bacteria replication and cell motility. Results from the studies will be published in peer-reviewed journals, presented at scientific meetings, and through public outreach events. This award is jointly supported by the Division of Biological Infrastructure and the Division of Molecular and Cellular Biosciences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.