Rheological Properties of Chromatin and Nuclear Microenvironment in Living Cells*

Genome organization and dynamics are essential in gene regulation and cellular functions. Chromosomal DNA wraps around histone octamers to form the basic functional unit, nucleosomes. Chromatin, a complex of multiple nucleosomes and proteins, is organized into a hierarchical structure which allows reconfigurable processes to occur during transcriptional regulation. The nuclear environment is a heterogeneous and viscoelastic medium, which constrains the transport of biological macromolecules, impacts the efficiency of enzymatic reactions, and influences chromatin folding and dynamics.  Investigation of chromatin and nuclear microenvironment viscoelasticity under physiological conditions has been a major challenge in the field. In this work, we use genomic-locus tracking and polymer models to characterize the viscoelasticity of chromatin and the surrounding nuclear environment. Specific genomic loci were imaged and tracked by CRISPR-based live-cell imaging techniques [1.2]. Elucidating the viscoelasticity of chromatin and its local microenvironment is a key to improving our understanding of human genome stability and nuclear function. This work demonstrates a new non-invasive approach to studying the local rheological properties of chromatin and nucleoplasm in the cell nucleus.