The Multiple Effects of Molecular Crowding in the Cell Nucleus: From Molecular Dynamics to the Regulation of Nuclear Architecture

Abstract The cell nucleus is a highly crowded environment. Indeed, this volume of few picoliters accommodates 2 m of genetic material as well as large amounts of different types of macromolecules such as RNAs or protein complexes. This high degree of macromolecular crowding is expected to strongly impact the dynamic behavior of biomolecules navigating through the nuclear volume. In this review, we present the consequences of crowding on molecular concentration, diffusion, and reaction equilibria which are predicted by theoretical and in vitro data. Next, we describe the experimental data that allowed quantitative assessment of the influence of macromolecular crowding on protein reaction-diffusion dynamics inside the nucleus. Finally, we review the recent findings investigating the different potential physiological roles of crowding. These results suggest that crowding is likely a central player in the control of the nuclear organization by affecting both the chromatin structure and the maintenance of the nuclear subcompartments. By regulating access to DNA, crowding may also affect all nuclear processes based on DNA transactions.