The functioning of human cells is akin to a city, requiring a precise transportation system to deliver various substances to the correct locations. However, the rapid speed of this transportation poses significant challenges for scientists studying it. Recently, a research team led by Professor Lin Yu-Chun from the Institute of Molecular Medicine developed a “RIVET system,” which acts like a cellular transportation control technique. By using light, this system can instantly halt specific transport vesicles within a cell, as if they were being "acupuncture-pointed," in just a few seconds.
The research team further validated this technology in experimental animals. Observations under a microscope revealed that nematodes, which are usually in constant motion, became completely still when illuminated with a specific wavelength of blue light. In this case, the synaptic vesicles responsible for transmitting neural signals in the cells were paused, reminiscent of being under a spell in the movie "Harry Potter." Once the light source was turned off, the nematodes resumed their movement as if the spell had been lifted, demonstrating that this technology can precisely and reversibly control the functioning of the nervous system.
Professor Lin noted that this breakthrough not only aids scientists in better understanding the mechanisms of life but also has potential applications in controlling insulin secretion, nutrient absorption, neural transmission, and even viral invasion, offering new hope for the treatment of various diseases. This research has been published in the prestigious journal Advanced Science.
The functioning of life relies on cells to transport various substances. Thousands of different transport vesicles travel along different pathways, akin to a complex and sophisticated logistics system. But how do these substances get to their destinations accurately? Professor Lin explains that cells encapsulate nutrients, hormones, and other substances in small vesicles and then utilize motor proteins to carry these vesicles along the cell's “microtubules,” which serve as highways to their correct destinations.
“The speed of transportation within cells is astonishing!” says Professor Lin. If the transport vesicles were scaled up to the size of a car, they could travel at speeds of up to 700 kilometers per hour, faster than high-speed trains. The RIVET system developed by Professor Lin functions like an emergency brake system for vehicles, allowing the transport vesicles to come to a complete halt in just 15 seconds.
Professor Lin mentioned that in previous studies investigating intracellular transportation systems, researchers had to either extract or inhibit the relevant molecules of the transporting vesicles to pause their movement for observation, a process that took three days and was highly inefficient. However, the team’s RIVET system resolves this issue by genetically modifying specific transport vesicles and microtubules to produce different “biological glues.” When illuminated with specific wavelengths of blue light, the vesicles and the tracks bind together like epoxy glue, effectively pausing their movement.
Professor Lin explained that controlling cellular transportation systems can also be achieved using chemical agents, but once added, these agents are difficult to eliminate and cannot be easily turned on or off. In contrast, the light-based method is more ideal: “Whoever is illuminated with light stops, and when the blue light is turned off, they resume movement; it’s as flexible as having a switch.”
The discovery of this technology was actually a serendipitous occurrence. While supervising a master's student, Chen Hsiao-Chi, Professor Lin discovered unexpected phenomena in the originally designed control group during their research. However, the research team turned this unexpected finding into a significant development.
“If we can control cells at will, there would be no diseases, and medicine would be unnecessary.” This is the grand vision of Professor Lin as a biomedical scientist. In fact, since developing the RIVET system, his team has applied it to numerous studies. For instance, the COVID-19 virus enters the human body through ACE2 vesicles; Professor Lin’s research team has successfully utilized the RIVET system to halt the transportation of ACE2 vesicles to block viral invasion.
In addition to controlling the cellular transportation of nematodes, the RIVET system can also be used to control other experimental animals, such as fruit flies and mice. More importantly, Professor Lin's team has discovered that aging is closely related to the functioning of intracellular transport. If we can control cellular transportation, it may provide new research directions for the treatment of aging-related diseases, viral infections, and neurological disorders.
NTHU website
《Advanced Science》