Precision light-controlled tissue engineering paves the way for advanced 2D and 3D cellular models

In two pioneering studies published in Nature Communications, researchers unveil novel light-based technologies to control cellular behaviour with unprecedented accuracy. Led by Mustafa Khammash, head of the Control Theory and Systems Biology Lab at D-BSSE, and Matias Zurbriggen at Heinrich-Heine University Düsseldorf, these studies showcase a great advancement in synthetic biology by using light to guide cell behaviour in engineered two- and three-dimensional tissues.

4-finger pattern formed by blue and green cells
Light-induced cell death in a spatial four-finger pattern. After 16 hours of continuous blue-light pattern illumination, the cells surrounding the ‘hand’ died and were stained blue. For details see Fig. 3 of the first study.  

The first study introduces µPatternScope, a new light-based technology for improving tissue engineering, which is the process of creating and manipulating cells to form functional tissues. µPatternScope combines advanced light control and cell engineering to shape 2D cell cultures more precisely. This precision is important for shaping tissues or structures in ways that are functionally relevant for medical applications. For example, making cells die at certain times, a process called apoptosis, can help sculpt tissues into desired shapes.

Combining hardware and software

Developed by Sant Kumar from the Khammash lab, µPatternScope projects high-resolution light patterns onto cultures of mammalian cells. These light patterns control genetically modified cells that respond to light, a technique called optogenetics. The system combines hardware (for projecting light) and software (to control both the light patterns and the microscope that captures how the cells are responding). This allows them to induce apoptosis at precise points in the cell culture, shaping it into the desired pattern.

portrait of Sant Kumar, D-BSSE
“The field of optogenetics has experienced significant growth in recent years, driving an increasing demand for technologies that facilitate its use in advanced synthetic biology applications. We have developed innovative tools that provide precise spatial and temporal control over the induction of specific morphogenesis effectors. Our research focuses on leveraging these tools to advance tissue engineering applications.”
portrait of Sant Kumar, D-BSSE
Sant Kumar, former doctoral student in the Control Theory and Systems Biology lab, now specialist for lab automation at D-BSSE

Interactive and dynamic cell patterning

An additional feature of µPatternScope is that this system can adjust in real-time based on how the cells are responding. This closed-loop feedback system enables even greater precision, continuously modifying the light patterns to achieve the target tissue shapes. The researchers demonstrated the system’s capabilities through a “tic-tac-toe” game, in which light-controlled apoptosis patterns created the classic game grid, highlighting the potential of µPatternScope for interactive and dynamic cell patterning.

By merging optogenetics, i.e. light-controlled biology, optical engineering and advanced software, this new tool can be a game-changer for tissue engineering and its translation into medical and research applications. It provides a powerful way to control cells in a very specific, dynamic manner, which could lead to more sophisticated and functional engineered tissues.

Light-induced controlled death of programmed cells

The second study takes optogenetic control in tissue engineering a step further. Using light-sensitive gene switches, the researchers modulate cellular behaviour both in flat (2D) and three-dimensional structures. They engineered tissues to respond to blue and red light, which could trigger specific genetic changes in the cells. For example, they light-controlled cellular processes such as cell death, cell adherence, and the growth pattern of cells, with great precision. The researchers successfully demonstrated the controlled initiation of cell necroptosis, a form of cell death, and WNT3A signalling, a pathway involved in cell development.

The team used special tools like patterned LED lights and lasers to apply light in very specific patterns and at precise times. This technology offers a high level of control over how cells grow and interact in lab-grown tissues. Thus far, studying cell communication and tissue formation in a controlled setting has been difficult to achieve with traditional methods.

This pioneering work opens up exciting possibilities for creating more accurate 3D tissue and organ models for research, which could have important applications of light-based genetic control in regenerative medicine and disease modelling.

Find the original articles in Nature Communications:

Kumar, S., Beyer, H.M., Chen, M., Zurbriggen*, M. D., and M. Khammash* (2024) external page Image-guided optogenetic spatiotemporal tissue patterning using μPatternScope. Nature Communications 15, 10469. https://doi.org/10.1038/s41467-024-54351-6

Beyer, H.M., Kumar, S., Nieke, M., Diehl, C. M. C., Tang, K., Shumka, S., Koh, C. S., Fleck, C., Davies, J. A., Khammash*, M., and M. D. Zurbriggen*. (2024) external page Genetically-stable engineered optogenetic gene switches modulate spatial cell morphogenesis in two- and three-dimensional tissue cultures. Nature Communications 15, 10470. https://doi.org/10.1038/s41467-024-54350-7


Learn about research in the Control Theory and Systems Biology lab led by Mustafa Khammash.

 

JavaScript has been disabled in your browser