Kong, D.-M. | bioRxiv Science

bioRxiv2024

Super-Resolution Axial Imaging for Quantifying Piconewton Traction Forces in Live-cells

Cell mechanics play a pivotal role in regulating numerous biological processes. While super-resolution microscopy enables the imaging of cellular forces in the lateral dimension with sub-10-nanometer resolution, achieving comparable resolution along the axial dimension remains a significant challenge. In this study, we combine metal-induced energy transfer (MIET) imaging with novel DNA-hairpin-based molecular tension probes (MIET-MTP) to map integrin-mediated mechanical forces with nanometer precision in the axial direction. MIET-MTP allows for the simultaneous observation of both the plasma membrane and forceexerting molecules in the axial dimension. Using this approach, we mapped axial integrin tension in focal adhesions and podosomes, alongside their corresponding plasma membrane height profiles, offering detailed insights into the structures involved in force transmission.

biophysics↗

bioRxiv2023

Metal-induced energy transfer (MIET) imaging of cell surface engineering with multivalent DNA nanobrushes

The spacing between cells has a significant impact on cell-cell interactions, which are critical to the fate and function of both individual cells and multicellular organisms. However, accurately measuring the distance between cell membranes and the variations between different membranes has proven to be a challenging task. In this study, we employ metal-induced energy transfer (MIET) imaging/spectroscopy to determine and track the inter-membrane distance and variations with nanometer precision. We have developed a DNA-based molecular adhesive called the DNA nanobrush, which serves as a cellular adhesive for connecting plasma membranes of different cells. By manipulating the number of base pairs within the DNA nanobrush, we can modify various aspects of cell-cell interactions, such as adhesive directionality, distance, and forces. We demonstrate that such nanometer-level changes can be detected with the MIET imaging/spectroscopy. Moreover, we successfully employ MIET to measure distance variations between a cellular plasma membrane and a model membrane. This experiment does not only showcase the effectiveness of MIET as a powerful tool for accurately quantifying cell-cell interactions, but does also validate the potential of DNA nanobrushes as cellular adhesives. This innovative method holds significant implications for advancing the study of multicellular interactions.

biophysics↗