Activity-driven tissue alignment in proliferating spheroids on arXiv

Bend and splay deformations in proliferating spheroids. (Image by the Authors of the manuscript.)
Activity-driven tissue alignment in proliferating spheroids
Liam Ruske & Julia Yeomans
arxiv: 2208.08258

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.

Presentation by Liam Ruske at Current and Future Themes in Soft & Biological Active Matter, 5 August 2022

The rate at which cells divide or die varies across 3D cell aggregates because cells are competing for resources in the environment. (Image by L. Ruske.)
Modelling the Dynamics of 3D cell aggregates
Liam J. Ruske, Julia Yeomans
Date: 5 August 2022
Time: 11:00 (CEST)
Place: Current and Future Themes in Soft and Biological Matter, Nordita


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.

Liam Ruske participates in Current and Future Themes in Soft & Biological Active Matter, 01-19 August 2022, Stockholm

Participants at the Nordita workshop in Stockholm. (Photo by Boyi Wang)

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.

Activity gradients in two- and three-dimensional active nematics

Spatial variations of active stress induce active torques, which aligns self-propelled defects along the gradient direction. Additionally there are also passive torques acting on defects induce by the elastic energy associated with deformations of the director field. The magnitude of active and passive torques acting on defects depends on defect type: While +1/2 defects (2D) and +1/2 disclination lines (3D) are dominated by active torque, twist-type disclination are subject to passive torques which aligns them in a way which minimizes the elastic energy of the system. (Illustration by Liam Ruske)
Activity gradients in two- and three-dimensional active nematics
Liam Ruske & Julia Yeomans
Soft Matter 18 5654-5661 (2022)
arxiv: 2206.06499
DOI: 10.1039/D2SM00228K


We numerically investigate how spatial variations of extensile or contractile active stress affect bulk active nematic systems in two and three dimensions. In the absence of defects, activity gradients drive flows which re-orient the nematic director field and thus act as an effective anchoring force. At high activity, defects are created and the system transitions into active turbulence, a chaotic flow state characterized by strong vorticity. We find that in two-dimensional (2D) systems active torques robustly align +1/2 defects parallel to activity gradients, with defect heads pointing towards contractile regions. In three-dimensional (3D) active nematics disclination lines preferentially lie in the plane perpendicular to activity gradients due to active torques acting on line segments. The average orientation of the defect structures in the plane perpendicular to the line tangent depends on the defect type, where wedge-like +1/2 defects align parallel to activity gradients, while twist defects are aligned anti-parallel. Understanding the response of active nematic fluids to activity gradients is an important step towards applying physical theories to biology, where spatial variations of active stress impact morphogenetic processes in developing embryos and affect flows and deformations in growing cell aggregates, such as tumours.

Liam Ruske presented a poster at the Active and Intelligent Living Matter conference, 26 June – 1 July 2022, Erice, Italy

The beatiful view from the conference centre on Mount Cofano. (Photo by L. Ruske)
Between the 26th of June and the 1st of July 2022 Liam participated in the Active and Intelligent Living Matter conference on Sicily, where he presented a poster summarizing several of his research projects about active continuum theories and their application to biological systems.

Liam Ruske gives a talk at the CECAM Computational methods and tools for complex suspensions workshop, 23-27 May 2022, Bilbao, Spain

Between the 23rd and the 27th of May 2022 Liam participated in the CECAM workshop on Computational methods and tools for complex suspensions to present some of his work. In his talk titled “Modelling biological matter as active nematic fluids” he highlighted how numerical simulations of active fluids can be used to study the self-organization of three-dimensional tissues in a variety of biological systems, where a continuous influx of energy on a single-cell level drives striking collective behaviour at the tissue scale.

Round Table on the Universality of Active Matter: from Biology to Man-made Models

A screenshot taken during the round table discussion of 20 September 2021.

On the 20th of September, the last round table of the Initial Training on Theoretical Methods took place. The discussion was let by the ESRs David, Sandrine, Liam, Carolina, Danne, and Laura. We were excited by the presence of an inspiring panel composed of Felix Ritort, Roberto Cerbino, Kirsty Wan, Fabio Giavazzi, Bernhard Mehlig, and François Nédélec.

The quote “If a system is in equilibrium, it’s probably death” ignited a lively and dynamic discussion around the topic of this final round table: “The universality of active matter: From biology to man-made models.”
Several topics were discussed ranging from active matter length scales and entropy production, to the equipartition theorem and universality. The session left us pondering about the definition of active matter: From single cells to the galaxy, where does the definition of active matter end? Our panelists conclude that it all depend on the question we ask ourselves. The round table was closed with a highlight of the most interesting avenues and opportunities in active matter, including the merge information and activity, realization of in vivo systems, as well as the manipulation of soft matter systems. Some inspiring words from one of the panelists let us realize: “We are the future of active matter.”

Round Table Discussion on Introduction to Theoretical Active Matter

A screenshot taken during the round table discussion of 7 September 20201.

The first round table in the theoretical training gave a chance to start an interesting discussion which will continue in the following meetings.

The organizing ESRs were Ayten Gülce Bayram, Laura Natali, Liam Ruske, Jérémie Bertrand, Davide Breoni and Audrey Nsamela. They welcomed and introduced the three guests of the session: Nuno Araújo from the University of Lisbon, Jan Wehr from the University of Arizona and Denis Bartolo from École normale supérieure de Lyon.

The round table started with a personal question to the speakers about their interests and motivations for working in theoretical active matter. Having different backgrounds, the answers were very different, Nuno was attracted by non-intuitive behaviors observed in active matter experiments, while Jan started from a purely mathematical point of view and then moved towards physics of active systems. Denis provided another motivation, being head of a lab that deals with both theory and experiments.

The following discussion focused on the interaction and hierarchy between theory, simulations, and experiments. They all agree that establishing a constructive collaboration with experimental groups is not easy, but at the same time, it can have many benefits for both sides. However, none of the three elements is necessary for the others: a good paper can be presenting a theory not connected with experiments, even if its possible applications are not foreseeable yet. Denis firmly pointed out the difference between the observations and the tools (theoretical, numerical, and experimental) employed to explain it.

We also had a few more specific questions for the speakers, such as the distinctions in thinking between mathematicians and theoretical physicists, the possible applications to financial markets, and the differences in modeling artificial flocks and human crowds, which are often controlled by non-hydrodynamic variables.

We concluded the meeting by asking every one of our guests their tips for communicating the theory of active matter to a larger public. Here the answers were more relaxed and can be summed up as: trying to avoid technical and mathematical details while explaining the importance of the research problems, also using more familiar examples such as simulations employed in animation movies.

The Active Matter network has a new logo !

New ActiveMatter logos: color and BW version. (Image by ActiveMatter ESRs)
With a joint effort of the ESR students, a new logo for the ActiveMatter website was designed. The idea started as a handdrawing on a piece of paper and was quickly adapted to a better version with drawing softwares. More than 15 logos were suggested and submitted to a vote. The competition was fierce but we all came to agree on one of them and we are happy to present you the new official logo of the ITN ActiveMatter !

Morphology of active deformable 3D droplets published in Physical Review X

3D droplets composed of active matter change their shape in response to a continuous influx of energy. Active droplets display an unprecedented range of complex morphologies, from cup-shaped droplet invagination, run-and-tumble motion or surface wrinkles caused by contractile activity, to the continuous formation and retraction of finger-like protrusions driven by extensile activity.
Morphology of active deformable 3D droplets
Liam J. Ruske, Julia M. Yeomans
Phys. Rev. X 11, 021001 (2021)

We numerically investigate the morphology and disclination line dynamics of active nematic droplets in three dimensions. Although our model incorporates only the simplest possible form of achiral active stress, active nematic droplets display an unprecedented range of complex morphologies. For extensile activity, fingerlike protrusions grow at points where disclination lines intersect the droplet surface. For contractile activity, however, the activity field drives cup-shaped droplet invagination, run-and-tumble motion, or the formation of surface wrinkles. This diversity of behavior is explained in terms of an interplay between active anchoring, active flows, and the dynamics of the motile disclination lines. We discuss our findings in the light of biological processes such as morphogenesis, collective cancer invasion, and the shape control of biomembranes, suggesting that some biological systems may share the same underlying mechanisms as active nematic droplets.