Now, researchers at the Massachusetts Institute of Technology (MIT) have bioengineered starfish cells to trigger shape-changing movements with light. This discovery breaks open new directions for researching cell growth and development. Led by senior author Nikta Fakhri, an associate professor of physics, the study utilizes a newly developed framework involving the GEF enzyme and Rho protein to manipulate cell movements in real time. The research was recently published in the journal Nature Physics. These advances provide scientists with a new, noninvasive optical tool for manipulating and controlling the shape of a cell at its earliest developmental stages.
The research team decided to study starfish because of its radial symmetry and developmental characteristics. Among the authors on the team were first author Jinghui Liu, Yu-Chen Chao, and Tzer Han Tan. Their strategy involved injecting one of these light-sensitive GEF enzymes into egg cells from a single starfish ovary. With this action the researchers effectively triggered morphological transformations of the cells. This innovative approach makes it possible to enhance or inhibit specific cellular functions with pinpoint accuracy by exposing cells to light of different wavelengths.
A New Framework for Understanding Cell Dynamics
A central focus of Fakhri’s lab at MIT, he said, is understanding the underlying physical mechanics that control how a cell grows and journeys through development stages. So the five-limbed starfish proves an especially perfect organism for probing these big questions about growth, symmetry, and early development. According to Fakhri, "A starfish is a fascinating system because it starts with a symmetrical cell and becomes a bilaterally symmetric larvae at early stages, and then develops into pentameral adult symmetry."
The researchers constructed an optogenetic, light-sensitive version of the GEF enzyme using well-known methods. This enzyme naturally circulates in a cell's cytoplasm and plays a crucial role in regulating cell mechanics by interacting with the Rho protein. Activated by light, the GEF enzyme recruits Rho more precisely to a focal site in the cell, speeding up shape changes.
"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," said Nikta Fakhri.
Light-Driven Manipulation of Cell Shape
Our study demonstrates that we can control cell behaviors through the controlled expression of the GEF enzyme in the cell. Together, these discoveries create new opportunities for influencing cellular behavior. When scientists shine specific wavelengths of light on the enzyme, it gets to work. This activation recruits a protein called Rho to contractile structures, causing localized contractions. The greater the amount of GEF enzyme inserted into a cell, the stronger these contractions are.
"So there's all these signaling processes that happen along the way to tell the cell how it needs to organize," Fakhri explained.
This cutting edge dynamic field modeling approach provides amazing insight into how complex living systems self-organize and evolve their shapes. Fakhri notes that the research provides a template for building new kinds of “programmable” synthetic cells. These innovations have the potential to make a huge difference in future biomedical applications.
"This work provides a blueprint for designing 'programmable' synthetic cells, letting researchers orchestrate shape changes at will for future biomedical applications," stated Fakhri.
Implications for Future Research
The findings from this study arm researchers with transformative tools to help unlock mechanisms of growth and development. By learning from nature’s approach to solving these intricate problems, scientists can hope to reproduce them or take advantage of them in countless ways.
"The power of these tools is that they are guiding us to decode all these processes of growth and development, to help us understand how nature does it," Fakhri emphasized.
What’s really got Fakhri’s team excited though is the possibility of hacking cellular circuitry to produce the mechanical responses they want. Surprisingly, the Rho-GEF circuitry turned out to be a profoundly excitable system in which a small stimulus could produce disproportionate responses.
"We realized this Rho-GEF circuitry is an excitable system, where a small, well-timed stimulus can trigger a large, all-or-nothing response," said Fakhri.