Research

Seeing is Believing!

High-Speed Atomic Force Microscopy (HS-AFM)

HS-AFM is an innovative and cutting-edge tool in the realm of biomedical research, offering unprecedented insights into the nanoscale world of biological systems. HS-AFM's real-time imaging and force-sensing capabilities provide quantitative data on molecular interactions, cellular mechanics, and structural changes, furthering our understanding of the fundamental mechanisms underpinning life. It has the potential to uncover new insights into disease processes, aiding in the development of novel treatments and therapies. We develop HS-AFM techniques to visualize biomolecules' structural and functional dynamics in physiological-relevant conditions at high spatial and temporal resolution (~1 Å in vertical and ~1 nm in lateral directions; >10 frames per second).

Specifically, the Lin group is interested in HS-AFM Imaging, Line-Scanning, Point-Scanning, Force Spectroscopy, and correlative AFM modes.

Structural and Functional Correlation of Membrane Proteins

Membrane proteins play an essential role in maintaining the homeostasis of cells by functioning as transporters for signal transaction and energy conversion, among other functions. Therefore, knowledge of the atomic resolution structures of membrane proteins is extremely crucial to understanding their functions. Compared to electron and fluorescence microscopy, HS-AFM offers high temporal and spatial resolution simultaneously for imaging biomolecules in aqueous conditions. We develop HS-AFM techniques along with functional measurement tools to understand the structural and functional correlation of membrane proteins in close-to-native environments. 

Our current research interests include Transmembrane Proteins: Channels, Transporters, Receptors, Toxins, Porins, Enzymes, and Peripheral Membrane proteins

Extracellular side of outer membrane protein F (OmpF)
Dynamic ds-DNAs on mica

Protein-Nucleic Acid Interactions

Protein and nucleic acid interactions are vital to cellular processes. For example, proteins associated with nucleic acids can mediate the transcription and translation of DNA and RNA, and then decode the information carried by genetic material. In addition, protein-nucleic acid interactions are required to maintain the integrity of DNA and RNA throughout generations. To do so, proteins interact with nucleic acids in processes such as DNA replication, repair, and processing, as well as RNA processing and translocation. Using HS-AFM, we aim to gain the mechanistic view of protein-nucleic acid interactions at the single molecular level.

Our current research interests include CRISPR-Cas complexes, Transcription Factors, and Transposons. 

Instrument & Software Development

Compared to electron and fluorescence microscopy widely used in biology, HS-AFM is still a young biophysical and bioanalytical technique. To improve the performance of our HS-AFMs, we develop various signal processors and controllers. In addition to instrument development, we also develop novel algorithms and artificial intelligence methods to characterize the structural dynamics of our targeted biomolecules. 

Our current research interests include new Feedback Control Systems, Image Processing and Data Analysis, Molecular Recognition, and Kinetic & Biophysical Modeling.