Roughness and dynamics of proliferating cell fronts as a probe of cell\u2013cell interactions

Guillaume Rapin,Nirvana Caballero,Patrycja Paruch,Benedikt Ziegler,Audrey Rawleigh,Iaroslav Gaponenko,Ermanno Moriggi,Steven A Brown,Thierry Giamarchi

doi:10.1038/s41598-021-86684-3

Guillaume Rapin, Nirvana Caballero + Show 7 more

Open Access

https://doi.org/10.1038/s41598-021-86684-3

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Abstract

Juxtacellular interactions play an essential but still not fully understood role in both normal tissue development and tumour invasion. Using proliferating cell fronts as a model system, we explore the effects of cell–cell interactions on the geometry and dynamics of these one-dimensional biological interfaces. We observe two distinct scaling regimes of the steady state roughness of in-vitro propagating Rat1 fibroblast cell fronts, suggesting different hierarchies of interactions at sub-cell lengthscales and at a lengthscale of 2–10 cells. Pharmacological modulation significantly affects the proliferation speed of the cell fronts, and those modulators that promote cell mobility or division also lead to the most rapid evolution of cell front roughness. By comparing our experimental observations to numerical simulations of elastic cell fronts with purely short-range interactions, we demonstrate that the interactions at few-cell lengthscales play a key role. Our methodology provides a simple framework to measure and characterise the biological effects of such interactions, and could be useful in tumour phenotyping.

Highlights

Juxtacellular interactions play an essential but still not fully understood role in both normal tissue development and tumour invasion
We report on the roughness and dynamics of such a 2D system: propagating Rat[1] fibroblast cell fronts studied in an in-vitro scratch assay over multiple orders of lengthscales and several days, with and without pharmacological modulation targeting cell division rate, cell motility and mechanical intracell and intercell force transmission, as well as certain types of cell–cell communication
Calculating the roughness function B(r) = | u(r.z)|2 for each front allows us to extract the roughness exponent ζ and its evolution with time, while the average displacement of the front u(z) with respect to the initial position allows us to extract the front dynamics. Both the roughness and dynamics are highly reproducible for a given set of conditions, as discussed in SI 5

Summary

Introduction

Juxtacellular interactions play an essential but still not fully understood role in both normal tissue development and tumour invasion. We find two different regimes of power law scaling in the cell front roughness, with distinct values of the exponent: below the average cell size ζ ≈ 0.58 for all conditions, and between 5 to 10 cells, ζ varies from 0.13 to 0.25, with a marked effect of pharmacological modulation.

Results

Conclusion