Cell: Scientists develop new super-resolution imaging technology to reveal new phenomena in organelle interactions

Li Dong's research group from the Institute of Biophysics of the Chinese Academy of Sciences, in cooperation with Eric Betzig and Jennifer Lippincott Schwartz, Ph.D. from the Howard Hughes Medical Research Institute in the United States, published a research paper "Visualizing intelligent organization and cytoskeleton interactions at nanoscale resolution on millisecond timescales" in the journal Cell. This article introduces the grazing incidence structured light illumination super-resolution imaging technology (GI-SIM), which can perform high-speed, long-term, and super-resolution imaging of physiological processes within cells. Using this technology, various new behaviors of organelle interactions have been discovered.

GI-SIM can continuously image nearly 10000 super-resolution images of live cells at a resolution of 97 nanometers and an imaging speed of 266 frames per second. Compared with the total internal reflection structured light illumination super-resolution imaging technology (TIRF-SIM; Li et al., Science, 2015) previously developed by Li Dong, GI-SIM has increased the imaging depth and generated signal volume by 10 times; Compared with traditional confocal or rotary confocal microscopes, GI-SIM can provide 2 times higher spatial resolution and 10 times faster imaging speed; Compared with other super-resolution imaging techniques, GI-SIM can provide up to 10 times faster imaging speed and 10-100 times longer imaging duration within the field of view of cell size. GI-SIM has achieved optimized two-dimensional super-resolution imaging of various organelle dynamics within cells, enabling researchers to discover new behaviors of organelle interactions. For example:

(1) Three novel ways of extending the tubular endoplasmic reticulum.

The formation of the network structure of endoplasmic reticulum is achieved through the continuous extension and fusion of tubular endoplasmic reticulum. Previous research has pointed out that there are two ways of extending the tubular endoplasmic reticulum: sliding and microtubule aggregation end co growth (pTAC). This study found three ways of extending the tubular endoplasmic reticulum: microtubule depolymerization end traction (dTAC), hitchhiking, and microtubule independent (Budding).

(2) The interaction between mitochondria and endoplasmic reticulum affects the division and fusion of mitochondria.

The division of mitochondria is closely related to the endoplasmic reticulum, and statistics have shown that approximately 85% of mitochondrial division events occur at contact sites between mitochondria and the endoplasmic reticulum. Further research has found that approximately 60% of mitochondrial fusion events occur at the contact sites between mitochondria and the endoplasmic reticulum, and mitochondrial fusion events that come into contact with the endoplasmic reticulum are usually faster than those that do not.

(3) Multi color GI-SIM imaging revealed that lysosome endoplasmic reticulum interaction plays a crucial role in regulating the dynamic transport and distribution of lysosomes within cells.

(4) Previous studies have only found that the endoplasmic reticulum can change its network structure through fusion, while this study observed that lysosomes in motion can cause transient rupture of the tubular endoplasmic reticulum.

(5) This study confirmed the widespread "hitchhiking" interactions between different organelles in mammalian cells, and observed that morphological changes and migration of organelles such as mitochondria and endoplasmic reticulum can be achieved by loading onto other moving organelles without directly recruiting motor proteins.

Guo Yuting, a doctoral student in Li Dong's research group, and Li Di, an assistant researcher, are co authors, while Zhang Siwei, a doctoral student, is the second author. Li Dong, Eric Betzig, and Jennifer Lippincott Schwartz are co corresponding authors. The research group led by Liu Jiajia from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and the research group led by Dan Kiehart from Duke University participated in this project. (Biological Valley)