Activity-driven tissue alignment in proliferating spheroids
Liam Ruske & Julia Yeomans
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.
Between the 2nd and the 5th of August David participated in the Complex Nanophotonics Science Camp in Windsor, UK. The Science Camp brought together 60 early-career scientists in the field of photonics but also science writers and editors in an unconventional format – mixing contributed and invited talks, seminars and debates – to present and discuss the latest research and future directions of the field in an open atmosphere and help developing the Complex Nanophotonics community. During this conference David presented a talk on “Elongated active particles in speckle fields“, the questions were many and the community was very interested in the topic. In the journey to Windsor, David visited Phil and Giorgio’s lab, which was a great opportunity to discuss with the other students in the groups.
Multicellular spheroids are self-assembled balls of cells, typically hunderds of microns in diameter. They are important model systems for high throughput screening of the effects of mechanical or oxidative stress on tumors and for testing the efficacy of anti-cancer drugs. Gradients in metabolite concentration and the cell division rate across spheroids lead to gradients in activity, the rate at which the cells use energy to generate forces. This results in cell ordering and flows that can be described using the theories of active nematics. By comparing cell alignment profiles in experiments to model predictions, we can extract dynamical tissue parameters which are difficult to measure directly, thus establishing a link between 3D active fluids and the tissue-scale organization in biological systems.
Between the 1st and the 19th of August 2022 Liam participated in the Nordita workshop Current and Future Themes in Soft & Biological Active Matter. In his talk titled “Modelling the Dynamics of 3D cell aggregates” he motivated how cell divisions and death act as a source of active forces in cellular aggregates and how these processes can be incorporated into continuum models of tissues. Applying this model to 3D living cell aggregates (spheroids) not only allows the inference of 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.