by Dr. Rakesh Das, Max-Planck-Institute for the Physics of Complex Systems, Dresden, Germany

Abstract:

Living matter exhibits striking spatiotemporal patterns that emerge from the interplay of its soft and active components. Unlike equilibrium systems, these patterns are sustained by a continuous influx of energy at local scales, which breaks time-reversal symmetry locally and thereby drives active behaviors. In this talk, I will discuss how multiscale coordination among soft and active matter can shape the spatiotemporal organization of biological (eukaryotic) cells.

First, I will present a physical model capturing the experimental observation that a DNA–protein co-condensate, triggered by a double-strand DNA break, can tether the broken ends—an essential step in the cell’s DNA damage response. Combining simulations with simple theoretical models, I will show that a kinetic competition between the DNA polymer’s recoil dynamics and the DNA–protein condensation kinetics governs reliable tethering [1]. Next, I will introduce a model for active inter-segmental crossings in polymers, as occurs naturally inside the cell nucleus, and demonstrate how this activity gives rise to anisotropic phase separation features of chromatin (i.e., the functional form of DNA) that cannot be explained by equilibrium physics [2]. I will then show how such active perturbations influence the dynamics of an embedded probe within this polymeric medium and identify the underlying physical mechanism [3]. Finally, I will highlight experimental evidence of mechanical coupling between the sub- and extranuclear medium and outline a systematic strategy to explore multi-scale coordination among such active media, which is essential to cellular function [1–5].

References:

1. RD, Tarun Mascarenhas, Nagaraja Chappidi, Simon Alberti, and Frank Jülicher, Break-induced DNA-protein condensate tethers broken ends, manuscript drafted.
2. RD, Takahiro Sakaue, G. V. Shivashankar, Jacques Prost, and Tetsuya Hiraiwa, How enzymatic activity is involved in chromatin organization, eLife 11, e79901 (2022).
3. RD, Takahiro Sakaue, G. V. Shivashankar, Jacques Prost, and Tetsuya Hiraiwa, Chromatin remodeling due to transient-link-and-pass activity enhances subnuclear dynamics, Phys. Rev. Lett. 132, 058401 (2024).
4. RD, Manoranjan Kumar and Shradha Mishra, Polar flock in the presence of random quenched rotators, Phys. Rev. E 98, 060602(R) (2018).   
5. F. Lottersberger et al., 53BP1 and the LINC complex promote microtubule-dependent DSB mobility and DNA repair, Cell 163, 880 (2015).