Institute for Medical Informatics, Statistics and Epidemiology – University of Leipzig
Swarm intelligence in tissue formation – the tale of the gut
Tissues of the outer surface like the skin and tissues of the inner surfaces as in the intestine have multiple functions. They protect against the invasion of foreign organisms and toxic chemicals and against loss of body fluid and cells. The gut also serves as an organ for taking in nutrients. The outer lining of these tissues (above the connective tissue) is covered by specialized cells called epithelial cells. They are tightly connected with one another to produce a dense spatial coverage. On the other hand epithelia are highly dynamic tissues. The epithelium of the human small intestinal gut is exchanged every 5 days, in the colon it lasts about 2-3 weeks and in the skin between days and weeks depending of the location and challenge. It has been found that the intestinal cell population residing in the intestinal crypts (ie pockets of cells embedded in the gut wall) have an impressive self-organization potential. A crypt with 300 cells can be fully regenerated from 1 cell after damage .
The understanding of the dynamic self-organization of the tissue has intrigued cell scientists for decades and the key mechanisms are getting slowly unraveled. We have recently demonstrated that one underlying principle of epithelial self-organization is swarm intelligence. Cells communicate with their neighbour cells and reactions are induced based on the communication. Cells process signals to their neighbors and receive signals from them. Depending on the status they find themselves in they react in different ways to these signals determining cell proliferation and cell differentiation. Cell biologists have perturbed communication signaling in many ways and the tissues reacted in deregulated ways. To understand whether the concept of swarm intelligence (ie simple rules of neighbor interactions explain the complex behavior of macroscopic swarms of birds, fish or insect states) we undertook computer simulations of the gut crypt. In the computer we created populations of cell agents in a 3D-crypt like structure. The agents can change their status (i.e. proliferative status, cell speciality, age) while signals are coming in signals are sent. We could show that this simple “socio-cellular” system has a great potential to explain a vast spectrum of observations and experiments. This understanding also has major implications of our understanding of tissue stem cells and their potential.
This finding indicates that the incredible complex genomic and epigenomic machinery is “invented” to make simple rules work. It is remarkable also that this system can tolerate a lot of damage to its individual components before it fails as a whole. We can speculate that evolution has selected these systems for their robustness against damage. I will illustrate the tale from the crypt with animated computer simulations created in my team of bioinformaticians in cooperation with cell biologists from any different laboratories.
In addition I suggest to play a game with all participants of the workshop in which we will experience the effect of rules on the movement of a group of persons and we will try to create a swarm ourselves.