New study opens doors for precise control of cells using light

Light is fundamental to human life—without it, we’d be hungry, cold and blind. But what if the same light that sustains us could also be used to control and observe parts of cells within our bodies?

Researchers at the Texas A&M Health Institute of Biosciences and Technology have developed a tool using a simple light to manipulate proteins and microtubules in the cells of the body, giving researchers new ways to observe progression and implications of complex diseases like cancer and dementia.

The study, published in Cell Reports Methods, was led by Yubin Zhou, MD, PhD, FAAAS, FAIMBE, FRSC, director of the Center for Translational Cancer Research at the Institute of Biosciences and Technology and professor in the Texas A&M Naresh K. Vashisht College of Medicine, together with Yun Huang, PhD, FRSC, professor and associate director of the Center for Epigenetics and Disease Prevention.

Microtubules are tiny structures within cells that make up microscopic highways that carry cargo; position cellular components; and coordinate signals that control how cells grow, divide and respond to stimulation, Zhou explained. Sometimes, for various reasons, these highways break down, causing a stall in traffic—like a train stopped on the tracks at a busy intersection.

While a stopped train will eventually be moved, it might take time for traffic patterns to resume normally, sometimes leading to a secondary fender bender. Similarly, in a microtubule, the impacts of a stall can lead to serious consequences. Disrupted microtubules have been linked to cancer and neurodegenerative diseases, like Alzheimer’s and dementia.

“Microtubules are not simply structural scaffolds; they are dynamic information and transportation networks that help organize nearly every aspect of cellular life,” Zhou said. “Our goal was to develop a unified way to control different dimensions of microtubule biology using something as simple and precise as light.”

Traditional avenues for studying microtubules rely on genetic modification, drugs or other methods that may disturb normal cell behavior, can be difficult to reverse and often lack precise control over changes, he said. The new approach developed by Zhou’s team deviates from previous methods by using CRY2—a light-sensitive protein found in plants that rapidly gathers into clusters when exposed to blue light.

The researchers paired the CRY2 protein with other proteins that already interact with or regulate microtubules and created tools that are inactive in normal circumstances but can be controlled when illuminated with a specialized blue light.

The blue light acts as a remote control for four tools: OptoMT, OptoTIP, OptoMotor and OptoSAW.

OptoMT gives light to the surrounding microtubule network, allowing scientists to view cargo traveling along the designated path, acting as streetlamps for those watching with the ability to turn on and off with no damage to the cell or structures inside it.

Acting like a construction spotlight on an unfinished road, OptoTIP allows scientists to observe the microtubules being built in real time, only highlighting the very end of the growing structure. While other similar tools change the structural and chemical features of microtubules, OptoTIP follows the growing ends of microtubules without causing changes to the behavior and stability of the structure.

OptoMotor is used to turn on molecular motors inside the cell to redirect cargo. Like a large shipping network, the microtubules are highways and OptoMotor functions as a very specific version of a delivery truck that becomes active with the blue light. When the OptoMotor gets the “go ahead” from the light, it will begin moving and scientists can utilize it to manipulate movement and even attach special cargo.

OptoSAW is like a pair of scissors that can be used to cut the microtubules with precision. While breaking the cellular highway may not seem useful, OptoSAW’s slices are fully reversible, allowing scientists to study what a broken or disconnected path may do to traffic and communication.

The tools move researchers into the driver’s seat, said Tien-Hung Lan, PhD, one of the lead authors of the study and postdoctoral fellow at the Center for Translational Cancer Research.

“The exciting part is that we are no longer limited to observing where things go inside a cell,” Lan said. “We can now ask causal questions: What happens if we move this organelle here, modify this part of the cytoskeleton there or disrupt a local microtubule network at a precise moment?”

The best thing about the new group of tools is that they leave no long-term impacts on the cell, so researchers could use them to learn more about what is happening on a microscopic level and develop treatments for a number of diseases and conditions, such as cancer and neurodegeneration—without risking permanent damage or alterations.

The tools are already available to researchers through Addgene, a nonprofit organization that helps scientists share and obtain genetic research materials, Zhou said. Looking ahead, the team hopes to adapt them for gene therapy studies—testing whether restoring damaged microtubule “highways” in neurons could help counter diseases such as Alzheimer’s, or whether deliberately disrupting these highways in cancer cells could help kill tumors.

“For the scientific community, this provides a set of very convenient tools,” Zhou said. “All you need to make it possible to express the cells is to just shine with our light, and now you can manipulate them. Previous methods could not be used on living cells, but now you can examine the microtubule networks in real time.”

By Lasha Markham, Texas A&M Health