Switching from electricity to light in stimulation-based therapy

Electrical stimulation can be used in medical applications like brain surgery to induce certain behaviors in the tissue, like neuron activation. Light can be a safer alternative to electrical stimulation, but living cells are not usually sensitive to light and must be modulated with phototransducers. Previous phototransducers used successfully on living cells, however, require gene modification, which significantly limits their real-world applicability. Vurro et al. developed a proof-of-concept that shows a molecule injected into a cell’s plasma membrane enables that cell to be excited by light.

The authors showed that molecular phototransducers can be used to trigger cardiac cell contraction using an photochromic compound called Ziapin2. The authors found that Ziapin2 molecules stay in the plasma membrane and, when illuminated, change conformation, causing the molecules to perturb the membrane and induce depolarization large enough to start a contraction in a cardiac cell.

“Our study shows that such molecular transducers are efficient tools for cell photostimulation, offering an alternative to optogenetics or electrical stimulation,” author Guglielmo Lanzani said.

In their study, the team grew a thin film of anisotropic cardiomyocytes on top of a flexible substrate. They observed that light induces a contraction of the cardiac cells, which in turn causes a macroscopic bending of the substrate.

Lanzani said their study serves as a model for similar systems and can be improved.

“Our molecular photo-transducers tend to leave the membrane with time, and their effect fades off. For application in vivo a prolonged action would be better suited,” Lanzani said. “Different excitation wavelengths would be useful for applications in soft robotics or medicine. Both improvements call for new chemical synthesis.”

Source: “Light-triggered cardiac microphysiological model,” by V. Vurro, K. Shani, H. A. M. Ardoña, J. F. Zimmerman, V. Sesti, K. Y. Lee, Q. Jin, C. Bertarelli, K. K. Parker, and G. Lanzani, APL Bioengineering (2023). The article can be accessed at https://doi.org/10.1063/5.0143409 .