Exploring (dry) active field theories (AMB+) to unravel solidification of protein condensates

The spatial organisation of proteins into dense condensates (L1), widely attributed to nonequilibrium phase separation, offers a route to recruit or sequester proteins involved in functions at the cellular level. However, our understanding of the underlying physical principles governing aggregation of large molecules in complex environments is still far from complete. For example, protein condensates are not necessarily stationary but can age into solid-like aggregates. As condensates become less liquid-like, they may lose their biochemical functionalities, which has been linked to neurodegenerative diseases [1]. This raises the question how biological cells prevent condensates from solidifying, and how to incorporate aging into models for condensates [2].

This project will investigate the physics of dynamic arrest in dense non-motile active matter to disentangle active contributions (due to chemically driven processes in the condensate) from the dynamic slowdown caused by repulsive (glass-like) and attractive (gel-like) interactions. We will extend minimal coarse-grained models (T1, T9) of protein aggregation to include chemically driven modulations of the pair-wise model interactions. Emphasis is placed on the thermodynamically correct modelling of chemically-induced transition rates (T7). Next, we will link these models to scalar active field theories [3, 4] (T3). Approaching dynamic arrest implies the emergence of memory, and we will explore connections to MCT (IRP 3.6) to solve for, and compare with, experimentally accessible correlation functions (e.g., FRAP).

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[1] Visser, BS, et al. (2024) Nat Rev Chem 8:686 [2] Takaki, R, et al. (2023) Phys Rev X Life 1:013006 [3] Robinson, JF. (2024) arXiv:2406.02409 [4] Zwicker, D. (2022) Curr Opin Colloid Interface Sci 61:101606