Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

Abstract
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Abstract

The coordination of cell proliferation and migration in growing tissues is crucial in development and regeneration but remains poorly understood. Here, we find that, while expanding with an edge speed independent of initial conditions, millimeter-scale epithelial monolayers exhibit internal patterns of proliferation and migration that depend not on the current but on the initial tissue size, indicating memory effects. Specifically, the core of large tissues becomes very dense, almost quiescent, and ceases cell-cycle progression. In contrast, initially-smaller tissues develop a local minimum of cell density and a tissue-spanning vortex. To explain vortex formation, we propose an active polar fluid model with a feedback between cell polarization and tissue flow. Taken together, our findings suggest that expanding epithelia decouple their internal and edge regions, which enables robust expansion dynamics despite the presence of size and history-dependent patterns in the tissue interior.

Data availability

Representative raw datasets for each Figure are available at Zenodo DOI: 10.5281/zenodo.3858845Full raw dataset is hundreds of gigabytes due to the video data and can be provided upon request. Key analysis code provided at our github repository: Github DOI: 10.5281/zenodo.3861843

Article and author information

Author details

Matthew A Heinrich

Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States

Competing interests
The authors declare that no competing interests exist.
Ricard Alert

Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1885-9177
Julienne M LaChance

Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States

Competing interests
The authors declare that no competing interests exist.
Tom J Zajdel

Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States

Competing interests
The authors declare that no competing interests exist.
Andrej Košmrlj

Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6137-9200
Daniel J Cohen

Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States

For correspondence
danielcohen@princeton.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5819-1135

Funding

National Institutes of Health (1 R35GM133574-01)

Daniel J Cohen

Human Frontiers of Science Program (LT000475/2018-C)

Ricard Alert

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.