This work could provide a blueprint for designing ‘programmable’ synthetic cells, letting researchers orchestrate shape changes at will.
The foundation of life begins with a single moving cell. Responding to biochemical signals, cells contract, shift, and divide, eventually organizing into complex living organisms. Now, researchers at MIT have discovered a way to manipulate these early cellular motions using light, providing a new tool to control cell shape and movement with remarkable precision.
This study deals specifically with the starfish egg cells, which are popularly used as a model organism to study cell behavior and development. The team was able to direct cellular movements such as contractions, pinches, and even shape transformations from circles into squares. This was done by genetically modifying the cell to have a light-sensitive enzyme and using focused patterns of light to stimulate cellular activities.“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,” says the study’s senior author Nikta Fakhri, associate professor of physics at MIT. “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.”Cracking the cellular motion code“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,” Fakhri says. “So there’s all these signaling processes that happen along the way to tell the cell how it needs to organize.”This research builds off earlier breakthroughs in understanding the architecture of a cell and the molecular circuitry that controls its movements.In this case, an enzyme named GEF is most important, and it is usually found in a cell’s cytoplasm. When GEF is active, it activates a protein called Rho, which has an affinity to the cell membrane. Rho protein participates in the development of muscle-like fibers which are very small. These fibers contract and allow the cell to alter its shape and position.Increasing GEF’s concentration within the cell led to increased contractions, and so this raised the question of whether it is possible to directly control how and when a cell moves using this molecular circuit.“This whole idea made us think whether it’s possible to hack this circuitry, to not just change a cell’s pattern of movements but get a desired mechanical response,” Fakhri says. Future biomedical applicationsOne particularly surprising finding was the discovery of an “excitability threshold” within the cell’s response system. The researchers observed that applying light to a single point on the cell, if the enzyme concentration was high enough, could trigger sweeping, whole-cell contractions.“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. “So we can either illuminate the whole cell, or just a tiny place on the cell, such that enough enzyme is recruited to that region so the system gets kickstarted to contract or pinch on its own.”To predict how cells would react to different light patterns, the team developed a theoretical framework that maps out cellular remodeling based on light stimulation. This is more than just a model; it gives a better understanding of fundamental biological phenomena such as embryo development and healing.“This work provides a blueprint for designing ‘programmable’ synthetic cells, letting researchers orchestrate shape changes at will for future biomedical applications,” she concludes.The study has been published in Nature Physics.
Biology Cell Response Cells Genetic Engineering Optogenetics Starfish
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