Few single-molecule experiments have enabled the direct imaging of functional biomacromolecules in real-time in their native liquid environments,resolving their conformational adaptations,transient interactions,and in...Few single-molecule experiments have enabled the direct imaging of functional biomacromolecules in real-time in their native liquid environments,resolving their conformational adaptations,transient interactions,and intermediate states.Liquid phase electron microscopy(LP-EM),due to its unique combination of spatial and temporal resolution,has shown to be a promising tool.Recent experiments have enabled successful imaging of intact structures of organic molecules and biological systems with an ordinary electron microscope.Adapting image processing methods and quantitative data analysis from single particle experiments based on the optical microscope,quantifying motion and relaxation of these interacting molecules allows the experimental observations of pathways,to test theoretical predictions,and discovery of new mechanisms.Combining LP-EM with tomography,fluorescence,and mass spectroscopy allows for probing multi-dimensional structural and dynamic information.Challenges remain in obtaining high-quality data in large quantities,which can be improved by developing new liquid cell platforms and machine learning-based data analysis.展开更多
基金H.W.thanks to the general support of the National Natural Science Foundation of China through funding 22174006the support of Beijing National Laboratory for Molecular Sciences,Center for Spectroscopy at Peking University.
文摘Few single-molecule experiments have enabled the direct imaging of functional biomacromolecules in real-time in their native liquid environments,resolving their conformational adaptations,transient interactions,and intermediate states.Liquid phase electron microscopy(LP-EM),due to its unique combination of spatial and temporal resolution,has shown to be a promising tool.Recent experiments have enabled successful imaging of intact structures of organic molecules and biological systems with an ordinary electron microscope.Adapting image processing methods and quantitative data analysis from single particle experiments based on the optical microscope,quantifying motion and relaxation of these interacting molecules allows the experimental observations of pathways,to test theoretical predictions,and discovery of new mechanisms.Combining LP-EM with tomography,fluorescence,and mass spectroscopy allows for probing multi-dimensional structural and dynamic information.Challenges remain in obtaining high-quality data in large quantities,which can be improved by developing new liquid cell platforms and machine learning-based data analysis.
基金supported by financial support from the National Key Research and Development Program of China(2021YFF1200200)the National Natural Science Foundation of China(22161132008)+2 种基金the Natural Science Foundation of Shanghai,China(19520714100 and 19ZR1475800)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SNZJU-SIAS-006)the Natural Science Foundation of Zhejiang Province(LQ21C050001)。
