Chromatin decompaction inside the nucleus increases plasma membrane tension and cell volume independently of transcription, according to a study published in Nature Communications. The findings demonstrate that chromatin acts as a direct regulator of whole-cell physical mechanics.
Researchers examined transcription-independent NETosis to evaluate whether nuclear chromatin organization dictates cellular mechanics. The team observed that chromatin accessibility gradually expanded during the process. Chromatin binding proteins H1, HP1α, and H3 dissociated from the decompacting chromatin structure at differential rates.
The study posited that the released chromatin binding proteins function as cellular osmolytes, shifting intracellular osmolarity. Adjusting extracellular osmolarity altered plasma membrane rupture and NETosis execution. Inhibiting specific cellular regulators of volume and membrane tension—including mTORC1/2, NHEs, and VRAC ion channels—produced comparable shifts in membrane rupture.
Tests on non-NETing U2OS cells showed that the mechanical effect operates across other cellular contexts. Decompacting chromatin within U2OS cells raised membrane tension without relying on the cytoskeleton, establishing a causal connection between chromatin organization and plasma membrane mechanics.
Aidan T. Cabral and Manasi Sawant contributed equally as lead authors on the paper alongside Minwoo Kang and Hawa Racine Thiam. The research was conducted across Stanford University, the Lerner Research Institute at the Cleveland Clinic, the Sarafan ChEM-H Institute, and the Chan Zuckerberg Biohub in San Francisco. Imaging was performed using a Leica Stellaris confocal microscope at the Stanford University Cell Sciences Imaging Core Facility.
