The Material Properties of the Cell Nucleus: A Matter of Scale.

Chromatin regulatory processes physically take place in the environment of the cell nucleus, which is filled with the chromosomes and a plethora of smaller biomolecules. The nucleus contains macromolecular assemblies of different sizes, from nanometer-sized protein complexes to micrometer-sized biomolecular condensates, chromosome territories, and nuclear bodies. This multiscale organization impacts the transport processes within the nuclear interior, the global mechanical properties of the nucleus, and the way the nucleus senses and reacts to mechanical stimuli. Here, we discuss recent work on these aspects, including microrheology and micromanipulation experiments assessing the material properties of the nucleus and its subcomponents. We summarize how the properties of multiscale media depend on the time and length scales probed in the experiment, and we reconcile seemingly contradictory observations made on different scales. We also revisit the concept of liquid-like and solid-like material properties for complex media such as the nucleus. We propose that the nucleus can be considered a multiscale viscoelastic medium composed of three major components with distinct properties: the lamina, the chromatin network, and the nucleoplasmic fluid. This multicomponent organization enables the nucleus to serve its different functions as a reaction medium on the nanoscale and as a mechanosensor and structural scaffold on the microscale.