The ability to control the behaviour of individual cells has long been a goal of scientists studying cell development. MIT researchers have now developed a method to manipulate how a single cell moves and changes shape, using light. This breakthrough, which could have far-reaching applications in synthetic biology and medicine, was demonstrated in egg cells from starfish—a common model for understanding cell behaviour during development.
The team, led by Nikta Fakhri, focused on an enzyme within the starfish egg cell that triggers a cascade of movements. By genetically engineering a light-sensitive version of this enzyme, the researchers were able to use light to direct the cell’s motion in precise patterns.
“We found that the light successfully triggered the enzyme, which in turn prompted the cells to jiggle and move in predictable patterns,” says Fakhri, an associate professor of physics at MIT. “For instance, we could stimulate cells to exhibit small pinches or sweeping contractions, depending on the pattern of light we induced. We could even shine light at specific points around a cell to stretch its shape from a circle to a square.”
The findings, set to be published in Nature Physics, open up exciting possibilities for future medical and synthetic cell applications. The researchers envision using this technology to design cells that could respond to light for therapeutic purposes, such as “patch” cells that contract to help close wounds or drug-delivering cells that release medication only when illuminated at specific locations in the body.
Fakhri continues, “By revealing how a light-activated switch can reshape cells in real time, we’re uncovering basic design principles for how living systems self-organize and evolve shape.”
The research team includes MIT’s Jinghui Liu, Yu-Chen Chao, and Tzer Han Tan, alongside collaborators from Ludwig Maximilian University of Munich, Saarland University, and the Whitehead Institute for Biomedical Research.
Exploring the Starfish Model
Fakhri’s group specializes in understanding the physical dynamics that drive cell growth, especially the role of symmetry in cell development. The starfish, known for its distinct stages of symmetry, is an ideal organism for studying the signalling processes that guide cell organization.
“A starfish is fascinating because it starts with a symmetrical cell and eventually develops into an adult with pentameral symmetry,” Fakhri explains. “There are many signalling events along the way that direct how the cell organizes itself into more complex structures.”
The team’s earlier research identified a key “circuitry” in the starfish egg cell that regulates its movement and shape. This circuitry involves an enzyme called GEF, which, when activated, triggers a protein called Rho. Rho plays a crucial role in regulating cell mechanics by binding to the cell’s membrane and initiating the formation of muscle-like fibres that enable the cell to contract and move.
Harnessing Light to Control Cell Movement
In this new study, the team turned to optogenetics, a technique that uses light to control genetically engineered cellular components. They created a light-sensitive version of the GEF enzyme and injected it into egg cells harvested from starfish. The cells, now capable of producing the light-sensitive enzyme, were placed under a microscope, and the researchers applied light in different patterns to observe how the cells responded.
By targeting specific areas of the cell with light, they were able to activate the enzyme, triggering the Rho protein to form fibers and cause the cell to move. This allowed the team to control the cell’s shape, even morphing it from a circle into a square. Additionally, they discovered that shining light in a single spot could initiate sweeping contractions within the cell, providing even more precise control over its behaviour.
“We realized this Rho-GEF circuitry is an excitable system, where a small, well-timed stimulus can trigger a large, all-or-nothing response,” Fakhri says. “By illuminating either the entire cell or just a small region, we can control how the cell responds and causes contraction or pinching.”
The researchers also developed a theoretical framework to predict how cells would change in response to light stimuli. This new understanding of cellular “excitability” could have important implications for fields like developmental biology, wound healing, and synthetic biology.
Future Applications in Synthetic Biology
“This work provides a blueprint for designing programmable synthetic cells,” Fakhri explains. “By controlling cell shape in real time, we can potentially design cells that perform specific tasks in the body when activated by light. This could lead to new biomedical applications, from targeted drug delivery to tissue repair.”
The ability to control cell behaviour with light opens up exciting possibilities for future research and applications, offering a new way to explore how cells shape themselves during development and how we might harness these processes for therapeutic use.