Professor Yi-Chih Lin of the University of Texas at Austin

"High-speed atomic force microscopy: A structural and dynamic tool for visualizing single-molecule biological processes"

High-speed atomic force microscopy (HS-AFM) has revolutionized molecular biophysics by enabling the dynamic visualization of biomolecules in action. This powerful technique allows real-time observation of protein dynamics and protein-nucleic acid interactions, offering unprecedented insights into molecular processes at single molecule level. Further advancements in environmental control—including temperature, force, and buffer conditions—and the development of fast-scanning submodes have expanded HS-AFM's applicability. It now permits the study of molecular motions with sub-nanometer spatial resolution and millisecond to microsecond temporal resolution. In the first part of my talk, I will demonstrate the capabilities of HS-AFM for modulating the conformational changes in the mechanosensitive Piezo1 ion channel in response to the application of force. The second part of talk will be focused on our recent advances in visualizing and analyzing protein-nucleic acid interactions. This includes investigating the topological dynamics of DNA and elucidating how the CTCF molecules (a transcription factor that marks topologically associated domain boundaries within the genome) regulate the DNA dynamics in loop extrusion, and other protein-nucleic acid interactions in gene editing and repair. These advancements in HS-AFM technology not only deepen our understanding of biomolecular dynamics but also offer new opportunities for integrating experimental insights with mathematical models, paving the way for breakthroughs in structural biology and its applications.