Activity-driven tissue alignment in proliferating spheroids

TL;DR

This paper extends active nematic fluid theory to model cell flows and tissue dynamics in spheroids, revealing how proliferation gradients influence cell alignment and identifying three distinct alignment regimes.

Contribution

It introduces a continuum model for tissue dynamics in spheroids that links proliferation gradients to cell alignment patterns, providing new insights into tumor mechanics.

Findings

Proliferation gradients induce specific flow and activity gradients.

Three distinct cell alignment regimes are identified.

Model enables inference of cell parameters from alignment profiles.

Abstract

We extend the continuum theory of active nematic fluids to study cell flows and tissue dynamics inside multicellular spheroids, spherical, self-assembled aggregates of cells that are widely used as model systems to study tumour dynamics. Cells near the surface of spheroids have better access to nutrients and therefore proliferate more rapidly than those in the resource-depleted core. Using both analytical arguments and three-dimensional simulations, we find that the proliferation gradients result in flows and in gradients of activity both of which can align the orientation axis of cells inside the aggregates. Depending on environmental conditions and the intrinsic tissue properties, we identify three distinct alignment regimes: spheroids in which all the cells align either radially or tangentially to the surface throughout the aggregate and spheroids with angular cell orientation close to the surface and radial alignment in the core. The continuum description of tissue dynamics inside spheroids not only allows us to infer dynamic cell parameters from experimentally measured cell alignment profiles, but more generally motivates novel mechanisms for controlling the alignment of cells within aggregates which has been shown to influence the mechanical properties and invasive capabilities of tumors.