The macroscopic limit to synchronization of cellular clocks in single cells of Neurospora crassa

Jia Hwei Cheong; Xiao Qiu; Yang Liu; Ahmad Al-Omari; James Griffith; Heinz-Bernd Schüttler; Leidong Mao; Jonathan Arnold

doi:10.1038/s41598-022-10612-2

The macroscopic limit to synchronization of cellular clocks in single cells of Neurospora crassa

Sci Rep. 2022 Apr 25;12(1):6750. doi: 10.1038/s41598-022-10612-2.

Authors

Jia Hwei Cheong^#¹, Xiao Qiu^#², Yang Liu¹, Ahmad Al-Omari³, James Griffith^{4

5}, Heinz-Bernd Schüttler⁶, Leidong Mao⁷, Jonathan Arnold⁸

Affiliations

¹ Chemistry Department, University of Georgia, Athens, GA, 30602, USA.
² Institute of Bioinformatics, University of Georgia, Athens, GA, 30602, USA.
³ Department of Biomedical Systems and Informatics Engineering, Yarmouk University, Irbid, 21163, Jordan.
⁴ Genetics Department, University of Georgia, Athens, GA, 30602, USA.
⁵ College of Agricultural and Environmental Sciences, University of Georgia, Athens, GA, 30602, USA.
⁶ Department of Physics and Astronomy, University of Georgia, Athens, GA, 30602, USA.
⁷ School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA, 30602, USA. mao@uga.edu.
⁸ Genetics Department, University of Georgia, Athens, GA, 30602, USA. arnold@uga.edu.

^# Contributed equally.

Abstract

We determined the macroscopic limit for phase synchronization of cellular clocks in an artificial tissue created by a "big chamber" microfluidic device to be about 150,000 cells or less. The dimensions of the microfluidic chamber allowed us to calculate an upper limit on the radius of a hypothesized quorum sensing signal molecule of 13.05 nm using a diffusion approximation for signal travel within the device. The use of a second microwell microfluidic device allowed the refinement of the macroscopic limit to a cell density of 2166 cells per fixed area of the device for phase synchronization. The measurement of averages over single cell trajectories in the microwell device supported a deterministic quorum sensing model identified by ensemble methods for clock phase synchronization. A strong inference framework was used to test the communication mechanism in phase synchronization of quorum sensing versus cell-to-cell contact, suggesting support for quorum sensing. Further evidence came from showing phase synchronization was density-dependent.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Diffusion
Lab-On-A-Chip Devices
Neurospora crassa*
Quorum Sensing