Statistical mechanics of motility and growth within extracellular matrices
Objectives
Collective cellular activity and self-organisation phenomena arising from non-equilibrium activity are ubiquitous in tissues and cellular aggregates. However, the relationship between individual properties and biological patterns remains unexplored due to overly simplifying assumptions embedded in classical active matter models. Cells crawl, swim, and squeeze through the extracellular matrix (ECM), as well as crawl over and pull on each other, while they proliferate [1]. In this project, we tackle this problem by introducing realistic forms of activity and the ECM environment, including crawling cell motility interactions with the network of the ECM that respect action-reaction. We focus on ECM, not only because its role is vital in cell biology but insufficiently understood, but also because of the strong medical interest for our industrial partner, Dyneval.
Activities of the Doctoral Candidate
Combining complementary approaches and expertises of the PIs–proliferating matter (Bittihn [2]), tissue models (Henkes [3,4]) and hydrodynamics (Shendruk) – we will systematically extend simple models of three-dimensional growing colonies, such as cancer spheroids [5], with additional biological mechanisms and develop new statistical mechanics tools appropriate for these inhomogeneously proliferating systems. This will take place in close exchange with our experimental collaborators (Pouyan Boukany / Gijsje Koenderink, Delft; Thomas Schmidt, Leiden). Preliminary results suggest the existence of signatures in collective behaviour that are distinct from ordinary self-propulsion included in state-of-the-art models. Preliminary simulations, using soft particles, are promising (picture: cells in blue, ECM in grey, cell polarisation shown as arrows). We will design tailored statistical mechanics measures to account for regulated division and apoptosis, since standard measures do not generalise to dividing particles and non-stationary dynamics, which will simultaneously benefit analysis of simulations and experimental differential dynamic microscopy measurements employed by Dyneval.
Facilities Provided
Access to computing facilities for numerical work, including high performance computing.
Employment Contract
Doctoral Candidate will be employed on a standard Dutch PhD researcher contract.
Period of Doctorate and Funding
Period of doctorate and funding: Doctorates at Leiden University take 4 years. A combination of department, Dutch funding agency NWO and unspent local CAFE-BIO funds will be used to support the Doctoral Candidate in year 4.
References
[1] Friedl, P, et al. (2009) Nat Rev Mol Cell Biol 10:445;
[2] Sunkel, T, et al. (2025) Commun Phys 8, 179;
[3] Henkes, S, et al. (2020) Nat Comm 11:1405;
[4] Kostanjevec K., et al. (2025), eLife14:RP106061, https://doi.org/10.7554/eLife.106061.1;
[5] van der Net, A, et al. (2024) iScience 27, 12, 111424