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A mathematical model reveals long-distance cell communication mechanism

October 15, 2019

How can tens of thousands of people in a large football stadium all clap together with the same beat even though they can only hear the people near them clapping?

A combination of a partial differential equation and a synthetic circuit in microbes answers this question. An interdisciplinary collaborative team of Professor Jae Kyoung Kim at KAIST, Professor Kresimir Josic at the University of Houston, and Professor Matt Bennett at Rice University has identified how a large community can communicate with each other almost simultaneously even with very short distance signaling. The research was reported at Nature Chemical Biology.

Cells often communicate using signaling molecules, which can travel only a short distance. Nevertheless, the cells can also communicate over large distances to spur collective action. The team revealed a cell communication mechanism that quickly forms a network of local interactions to spur collective action, even in large communities.

The research team used an engineered transcriptional circuit of combined positive and negative feedback loops in E. coli, which can periodically release two types of signaling molecules: activator and repressor. As the signaling molecules travel over a short distance, cells can only talk to their nearest neighbors. However, cell communities synchronize oscillatory gene expression in spatially extended systems as long as the transcriptional circuit contains a positive feedback loop for the activator.

Professor Kim said that analyzing and understanding such high-dimensional dynamics was extremely difficult. He explained, "That's why we used high-dimensional partial differential equation to describe the system based on the interactions among various types of molecules." Surprisingly, the mathematical model accurately simulates the synthesis of the signaling molecules in the cell and their spatial diffusion throughout the chamber and their effect on neighboring cells.

The team simplified the high-dimensional system into a one-dimensional orbit, noting that the system repeats periodically. This allowed them to discover that cells can make one voice when they lowered their own voice and listened to the others. "It turns out the positive feedback loop reduces the distance between moving points and finally makes them move all together. That's why you clap louder when you hear applause from nearby neighbors and everyone eventually claps together at almost the same time," said Professor Kim.

Professor Kim added, "Math is a powerful as it simplifies complex thing so that we can find an essential underlying property. This finding would not have been possible without the simplification of complex systems using mathematics."
The National Institutes of Health, the National Science Foundation, the Robert A. Welch Foundation, the Hamill Foundation, the National Research Foundation of Korea, and the T.J. Park Science Fellowship of POSCO supported the research.

Profile: Prof. Jae Kyoung Kim, PhD (twitter: umichkim)
Department of Mathematical Sciences
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon 34141, Korea

Profile: Prof. Kresimir Josic , PhD
University of Houston
Houston, USA

Profile: Prof. Matthew Bennett, PhD
Biosciences and Bioengineering
Rice University
Houston, USA


KAIST is the first and top science and technology university in Korea. KAIST was established in 1971 by the Korean government to educate scientists and engineers committed to industrialization and economic growth in Korea.

Since then, KAIST and its 61,125 graduates have been the gateway to advanced science and technology, innovation, and entrepreneurship. KAIST has emerged as one of the most innovative universities with more than 12,000 students enrolled in five colleges and seven schools including 1,000 international students from 80 countries.

On the precipice of its 50th anniversary in 2021, KAIST continues to strive to make the world better through the pursuit in education, research, entrepreneurship, and globalization.

The Korea Advanced Institute of Science and Technology (KAIST)

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