Living tissues are characterized by an intrinsically mechanochemical interplay of active physical forces and complex biochemical signaling pathways. Either feature alone can give rise to complex emergent phenomena, for example, mechanically driven glassy dynamics and rigidity transitions, or chemically driven reaction-diffusion instabilities. An important question is how to quantitatively assess the contribution of these different cues to the large-scale dynamics of biological materials. We address this in Madin-Darby canine kidney (MDCK) monolayers, considering both mechanochemical feedback between extracellular signal-regulated kinase (ERK) signaling activity and cellular density as well as a mechanically active tissue rheology via a self-propelled vertex model. We show that the relative strength of active migration forces to mechanochemical couplings controls a transition from a uniform active glass to periodic spatiotemporal waves. We parametrize the model from published experimental data sets on MDCK monolayers and use it to make new predictions on the correlation functions of cellular dynamics and the dynamics of topological defects associated with the oscillatory phase of cells. Interestingly, MDCK monolayers are best described by an intermediary parameter region in which both mechanochemical couplings and noisy active propulsion have a strong influence on the dynamics. Finally, we study how tissue rheology and ERK waves produce feedback on one another and uncover a mechanism via which tissue fluidity can be controlled by mechanochemical waves at both the local and global levels.
We thank all members of the Hannezo group for discussions and suggestions, as well as Sound Wai Phow for technical assistance. This work received funding from the European Research Council under the EU Horizon 2020 research and innovation program Grant Agreement No. 851288 (E.H.), JSPS KAKENHI Grant No. 21H05290, and the Ministry of Education under the Research Centres of Excellence program through the MBI at NUS.
Boocock DR, Hirashima T, Hannezo EB. Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. 2023;1(1). doi:10.1103/prxlife.1.013001
Boocock, D. R., Hirashima, T., & Hannezo, E. B. (2023). Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. American Physical Society. https://doi.org/10.1103/prxlife.1.013001
Boocock, Daniel R, Tsuyoshi Hirashima, and Edouard B Hannezo. “Interplay between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.” PRX Life. American Physical Society, 2023. https://doi.org/10.1103/prxlife.1.013001.
D. R. Boocock, T. Hirashima, and E. B. Hannezo, “Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers,” PRX Life, vol. 1, no. 1. American Physical Society, 2023.
Boocock DR, Hirashima T, Hannezo EB. 2023. Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. 1(1), 013001.
Boocock, Daniel R., et al. “Interplay between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.” PRX Life, vol. 1, no. 1, 013001, American Physical Society, 2023, doi:10.1103/prxlife.1.013001.
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