Mechanically Regulated Biphasic Chromatin Dynamics during Cellular Necrosis

Necrosis, long considered an uncontrolled and passive process, is now known to involve active cellular regulation. While significant research has focused on biochemical pathways of necrosis, the physical changes within the nucleus, particularly chromatin dynamics, remain unknown. By combining the single-particle tracking of telomeres and particle image velocimetry of global chromatin, we characterize the spatiotemporal evolution of chromatin dynamics during necrosis. We reveal a distinct biphasic pattern of chromatin motion with an initial deceleration followed by a late acceleration, accompanied by a transient increase and a subsequent decrease in intranuclear spatial heterogeneity. Through systematic perturbation, we establish a stage-specific regulatory model: the early deceleration of chromatin is driven by mechanical restraint from the cytoskeletal network, while the late acceleration results from the combined effects of nuclear swelling and DNA fragmentation. Our findings highlight necrosis as a programmed process, uncovering a previously unrecognized layer of cytoskeleton-mediated mechanical regulation in cell death.