Chromatin organization modulates cell mechanics​ beyond gene expression

Primarily studied for its role in gene expression, chromatin organization is emerging as an important regulator of nuclear mechanics. Here, we tested the hypothesis that as a dynamic crosslinked polymer, chromatin directly impacts cell mechanics independently of transcription by studying NETosis: a transcription-independent process where chromatin decompacts and the plasma membrane (PM) ruptures.

Using optical tweezers, we found that chromatin decompaction during NETosis increases PM tension, independently of the cytoskeleton. In non-NETing U2OS cells, we found a similar PM tension increase upon induced chromatin decompaction and disrupted cytoskeleton, suggesting that chromatin is a global mechanical integrator. We theorized that chromatin might regulate PM tension by generating cellular osmotic pressure. Lattice light sheet microcopy experiments indicate an increase in volume during NETosis and an increase in volume in non-NETing euchromatin-induced cells, supporting our theory. Our findings reveal a novel non-genetic role of chromatin in cellular biophysics: regulate PM tension, intracellular pressure and thus, overall cell mechanics.