A spindle-shaped muscle cell, a tree-like neuron, a disc-shaped blood cell, and a polygonal skin cell all arise from spherical stem cells. Cells have a dynamic ability to change their shape in tune with the needs of the organism; they elongate and pinch during division, deform in response to cues from surrounding cells during tissue formation, extend and retract protrusions to migrate during wound healing, and assume unique shapes to be able to perform specific functions, such as signal transmission in neurons.1 What are the rules that drive these transformations? Nikta Fakhri, a biophysicist at Massachusetts Institute of Technology (MIT), is trying to answer this question.
Nikta Fakhri, a biophysicist at Massachusetts Institute of Technology, studies the physical rules that drive cell growth and development.
Adam Glanzman
Scientists know that cell shape changes are regulated by complex networks of chemical reactions, but they have struggled to recapitulate these chemo-mechanical circuits in vitro to create synthetic cells.2 Now, in a recent study published in Nature Physics, Fakhri and her team engineered a light-activated enzyme to control the shape of starfish oocytes.3 This advancement could one day be applied towards regulated release of drugs and accelerated wound healing.
When Fakhri first worked with in vitro cellular systems during her postdoctoral research, she noticed certain challenges. “Reconstituted systems are very hard to get to the point that they do exactly what you see in living systems,” Fakhri said. So, when she established her own group at MIT, Fakhri was looking for a change. Serendipitously, a colleague next door was working on a unique animal model that has captured the interest of biologists since the 1800s: the starfish. “I love marine organisms. Their diversity in shape and behavior phenotypes is absolutely amazing,” Fakhri said.
An evolutionarily conserved chemical circuitry controls the shape of starfish egg cells. One of the key components of this network is the enzyme Rho guanine nucleotide exchange factor (Rho-GEF), which stimulates the growth and expansion of microscopic muscle-like fibers near the cell’s surface, thus creating local changes in cell shape.2 Fakhri and her colleagues engineered a system whereby they could control cell morphology through a light-activated variety of Rho-GEF. When they injected the modified Rho-GEF into starfish oocytes and illuminated specific points on the cell surface, they observed recruitment of actomyosin filaments towards the cell membrane at those locations, which led to localized shape changes. Using this method, they could modify cells to appear square or have tiny valleys and peaks in their membranes.
“People have been doing optogenetics for a couple of decades, but we tend to have a fuzzier understanding of what we're controlling,” said Amy Maddox, a cell biologist at the University of North Carolina at Chapel Hill, who was not involved in the study. “[Fakhri’s team] has reached a point with this tool where they're able to very accurately predict how their experiments will turn out.”
Fakhri still remembers the first time the team observed the light-induced shape changes. “It was just before Christmas and my student emailed a video of the cell saying, ‘This is a Christmas gift,’” she said. “It was amazing!” Unlike previous studies in which scientists have attempted to tinker with cell shape by optogenetically altering actomyosin fibers, targeting an upstream candidate provided Fakhri and her team with more control over the cell phenotypes.
The study is a jumping-off point for multiple avenues in the field of cell shape. “I imagine there will be adoption of both the theory and the optogenetic tool by people studying other cell shape changes like cytokinesis, cell motility, and cell-cell interactions,” Maddox said.
- Lecuit T, Lenne PF. Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis. Nat Rev Mol Cell Biol. 2007;8(8):633-644.
- Bement WM, et al. Activator–inhibitor coupling between Rho signalling and actin assembly makes the cell cortex an excitable medium. Nat Cell Biol. 2015;17(11):1471-1483.
- Liu J, et al. Light-induced cortical excitability reveals programmable shape dynamics in starfish oocytes. Nat Phys. 2025:1-10.
