Multi-cellular engineered living systems (M-CELS) are living machines and devices assembled from biological building blocks, such as living cells, organelles, proteins, nucleic acids, and biomaterials. In a review, Aydin et al. provide a set of primary design principles to guide the future development of M-CELS with an eye towards potential applications like biopharmaceuticals, biofuels, environmental bioremediation, and cellular computing.

“An analogy we use is this notion of robotics. A robot has many different components to it, whether it is wheels for locomotion, an arm for applying physical force, or a CPU for making decisions,” said author Ron Weiss. “The question is, can we do something similar in the field of biology? Can we make, essentially, biological robots?”

Although the field remains at an early stage, M-CELS have successfully moved from conceptual vision to laboratory demonstration. The researchers highlight three representative types of M-CELS: organoids, microphysiological systems, and biobots (biological robots). Established examples of M-CELS include human cortico-motor assembloids that accurately model the human corticospinal motor tract, biological pumps actuated by muscle, and an organoid liver derived from pluripotent stem cells.

“I’d like to one day have a computer-aided design tool that allows me to envision a 3D M-CELS, in the same way that you’d design a car or plane,” said Weiss. “Then I could press the ‘print’ button, and that M-CELS would be generated.”

No doubt, reaching such a point will require the field to overcome several challenges in the future. Indeed, creation of any M-CELS requires understanding the intrinsic and dynamic properties of multicellular systems. In addition, ethical concerns will play a role, with M-CELS complicating traditional notions of biological life and of the human.

Source: “Principles for the design of multicellular engineered living systems,” by Onur Aydin, Austin P. Passaro, Ritu Raman, Samantha E. Spellicy, Robert P. Weinberg, Roger D. Kamm, Matthew Sample, George A. Truskey, Jeremiah Zartman, Roy D. Dar, Sebastian Palacios, Jason Wang, Jesse Tordoff, Nuria Montserrat, Rashid Bashir, M. Taher A. Saif, and Ron Weiss, APL Bioengineering (2022). The article can be accessed at