Proliferating active media

While active matter theory has successfully advanced our understanding of the collective dynamics resulting from individual sources of activity, multiple active processes usually act in concert in real biological systems. This project will take a step towards understanding this complexity by considering multicellular systems (L3) with sustained proliferation and cell removal [1, 2] – such as tissues, bacterial colonies or tumors – as a background medium for single particles or cells with different properties (L2). We will combine the expertise of the PIs, namely proliferation simulations (Bittihn) (T1) [1–4] with continuum theories of active nematics (Shendruk) (T3, T4) [6-8] to unravel the statistical physics of these media and their two-way coupling with individual motile particles. This will elucidate how self-propulsion is modified by an active background and how immersed particles can in turn change the structure of the growing medium (L2, L3).

The dynamics of the medium itself is expected to be non-trivial due to the absence of number conservation and ancestral relationships between proliferating constituents, leading to generalisation of the concept of fluidisation that has been associated with cell turnover [9]. Preliminary evidence suggests that immersed motile particles – akin to foreign bodies or distinct cells – exhibit bi-directional coupling with the growing medium, accompanied by the creation of nematic defects (T5). We expect to substantiate such analogies. Matching large-scale particle-based simulations (T9, T10) to continuum theories will allow us to extract crucial parameters and general scaling behaviours, while at the same time maintaining a close connection to quantities that would be measurable in experiments, which could be tested in collaboration with experimental collaborators, such as the Betz lab in Göttingen, who are experts on embryogenesis and growing 3d cell colonies. Having established these two-way couplings, we will explore how feedback regulation of the growth process (e.g., via nutrient or pressure dependence) alters the statistical properties of the medium and immersed particles. Such principles might not only be exploited by biological systems but could also be harnessed to control the behaviour of artificial particles in biotechnological/medical applications or synthetic systems.

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[1] Isensee, J, et al. (2022) J Roy Soc Interface 19:20220512 [2] Pollack, YG, et al. (2022) New J Phys 24:073003 [3] Sunkel, T, et al. (2024) arXiv:2403.11002 [4] www.inparts.org [5] Lish SR, et al. (2024) arXiv:2409.20481 [6] Head, LC, et al. (2024) Nat Phys 20:492 [7] Keogh, RR, et al. (2024) Phys Rev Lett 132:188301 [8] Keogh, RR, et al. (2022) Phys Rev E 106:L012602 [9] Ranft, J, et al. (2010) Proc Natl Acad Sci 107:20863