Cells have an extraordinary ability: they dynamically reshape themselves, a process fundamental to vital activities like cell division and embryonic development. The study, published in Nature Physics, marks a significant step forward in our understanding of cell morphogenesis. The international research team, led by LMU physicist Erwin Frey, Chair Professor of Statistical and Biological Physics and member of the ORIGINS Excellence Cluster, and Nikta Fakhri at MIT, has unveiled the previously unknown mechanisms cells use to alter their shapes and managed to externally control these transformations using optogenetics—a method of genetically engineering cells to respond to light.

Illuminating Cellular Mechanics

Using oocytes (egg cells) from the starfish Patiria miniata, scientists genetically engineered enzymes responsible for cellular movements to become sensitive to light. “With these switches, we were able to arbitrarily modulate the protein distribution in the cell through light stimuli, which led to deformations,” says Tom Burkart, lead author of the study. Remarkably, the team could induce anything from local pinching to substantial reshaping of cells, even forming square-shaped cells from naturally round ones.

These cellular changes hinged upon two key enzymes: a small protein known as GTPase Rho and its activating enzyme GEF. When activated, GEF prompts Rho to bind to the cell membrane, initiating muscle-like fibers that cause cellular contractions. By embedding light-responsive molecular switches within GEF, researchers precisely activated these processes at specific cell locations.

Guided vs. Spontaneous Deformations

Beyond the impressive visual reshaping, researchers developed a theoretical model illustrating how these optical signals trigger cellular changes through chemical and mechanical interactions. They discovered two distinct modes: guided deformations localized to specific areas illuminated by targeted light and spontaneous, unguided shape changes triggered by stimulating just a single spot.

“We realized this Rho-GEF circuitry is an excitable system, where a small, well-timed stimulus can trigger a large, all-or-nothing response,” says Nikta Fakhri, associate professor of physics at MIT. This excitability underpins essential biological processes from embryo formation to tissue healing.

Implications for Synthetic Biology

The findings offer exciting potential for synthetic biology, paving the way toward synthetic cells that are programmable for specific biomedical purposes. Applications might include therapeutic cells engineered to contract and heal wounds under targeted illumination or carrier cells designed to release drugs precisely where needed.

“Our results show that living cells are much more versatile than previously assumed,” says Frey. Fakhri adds, “This work provides a blueprint for designing ‘programmable’ synthetic cells, letting researchers orchestrate shape changes at will for future biomedical applications.”

The study represents a powerful convergence of biology, physics, and genetic engineering, promising transformative advancements in medical therapies and bioengineering.