Mechanical stress affects dynamics and rheology of the human genome.

Abstract

Material properties of the genome are critical for proper cellular function - they directly affect timescales and length scales of DNA transactions such as transcription, replication and DNA repair, which in turn impact all cellular processes via the central dogma. Hence, elucidating the genome's rheology in vivo may help reveal physical principles underlying the genome's organization and function. Here, we present a novel noninvasive approach to study the genome's rheology and its response to mechanical stress inform of nuclear injection. Specifically, we use Displacement Correlation Spectroscopy [1] to map nucleus-wide genomic motions pre/post injection, during which we deposit rheological probes inside the nucleus [2]. While the former informs on the bulk rheology of the genome pre/post injection, the latter informs on the rheology of the probe's surroundings. Our results reveal that mechanical stress of injection leads to local as well as nucleus-wide changes in the genome's compaction, dynamics and rheology. We find that the genome pre-injection exhibits subdiffusive motions, which are coherent over several micrometers. In contrast, genomic motions post-injection become faster and uncorrelated, moreover, the genome becomes less compact and more viscous across the entire nucleus. In addition, we use the injected particles as rheological probes and find the genome to condense locally around them, mounting a local elastic response. Taken together, our results show that mechanical stress alters both dynamics and material properties of the genome. These changes are consistent with those observed upon DNA damage, suggesting that the genome experiences similar effects during the injection process [2].