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Ever since Robert Hooke first identified the cell in 1665, researchers have been using microscopes to delve deeper into these fundamental building blocks of life. Over the past 350 years, technological progress has enabled us to examine cellular functions more closely, though not all insights stem from direct observation. Certain cellular processes—such as the rapid formation of tiny bubbles on a cell's surface—occur too quickly for the human eye to detect, even with the most powerful microscopes. Much of this molecular activity has been deduced rather than directly observed.
Recently, scientists have developed a groundbreaking method to observe cellular processes in extraordinary detail, as showcased in a series of images published in the journal Science. These images unveil previously unseen aspects of cellular mechanisms, made possible by structured illumination microscopy (SIM), a technique borrowed from the film industry.
Two years ago, Harvard cell biologist Thomas Kirchhausen attended a lecture by Eric Betzig from the Howard Hughes Medical Institute’s Janelia Research Campus, where Betzig discussed the application of SIM in cellular studies. Betzig, who previously pioneered high-resolution microscopy using fluorescent markers to illuminate cellular components, shared the 2014 Nobel Prize in chemistry for his contributions.
A significant drawback of this approach is that it subjects cells to light intensities beyond their tolerance, often causing damage or even vaporization. In contrast, SIM offers a more delicate solution, enabling rapid imaging of live cells with minimal light exposure.
Kirchhausen envisioned applying SIM at the molecular scale to document cellular processes. Partnering with Betzig and researchers from China and the U.S., they produced a series of revolutionary images. One example is showcased in the video below, where magenta and green fluorescent markers illuminate the proteins actin (magenta) and myosin (green) collaborating to create the filament networks essential for cellular motion.
