Numerical simulations on how mechanical perturbations by subnuclear molecules can affect chromatin organization and dynamics

Rakesh Das^2,6, Takahiro Sakaue³, GV Shivashankar⁴, Jacques Prost^5,6, Tetsuya Hiraiwa^1,6*

¹Institute of Physics, Academia Sinica, Taipei, Taiwan
²Biological Physics, Max Planck Institute for Physics of Complex Systems, Dresden, Germany
³Department of Physical Sciences, Aoyama Gakuin University, Sagamihara, Japan
⁴Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
⁵Departement de Physicochimie du vivant, Institut Curie, Paris, France
⁶Mechanobiology Institute, National University of Singapore, Singapore, Singapore

* Presenter:Tetsuya Hiraiwa, email:thiraiwa@gate.sinica.edu.tw

Genetic information in a eukaryotic cell is stored in its chromatin, a polymer-like composite of DNA and proteins, densely packed within the nucleus. Physical spacing of chromatin is crucial in regulating gene transcriptions; meanwhile, in a living cell, other subnuclear molecules such as enzymes act to facilitate cellular functions. Mechanical perturbation due to such actions of molecules may affect the chromatin organization and dynamics. In this talk, I would like to explain our numerical-simulation studies about such effect, based on polymer-physics concepts and the GPU-aided computations, where we focused on a type of actions of molecules that we call catch-and-release action and implemented in the way inspired by a class of molecules like topoisomerase-II. Our simulation results demonstrate how it affects chromatin organization [1] and dynamics [2]. Refs. [1] R Das, T Sakaue, GV Shivashankar, J Prost, T Hiraiwa (2022) "How enzymatic activity is involved in chromatin organization", eLife 11, e79901. [2] R Das, T Sakaue, GV Shivashankar, J Prost, T Hiraiwa (2024) “Chromatin Remodeling Due to Transient-Link-and-Pass Activity Enhances Subnuclear Dynamics", Physical Review Letters 132, 058401.

Keywords: Chromatin physics, Microphase separation, Fluctuating dynamics, Numerical simulation