Mechanics of the vimentin juxtanuclear cage

Vimentin is a cytoskeletal protein that assembles a cage like structure around the nucleus called the juxtanuclear cage. While this is a curious cytoskeletal architecture, the mechanical interplay between the vimentin juxtanuclear cage and the nucleus remain virtually obscure. Our recent experimental evidence unveils a striking mechanical response where vimentin, a filamentous network known to be highly entangled with actin and microtubule spanning the cytoplasm, exhibits a differential stress relaxation when subject to micropipette aspiration. In these experiments, we show that the vimentin juxtanuclear cage remains tightly bound to the nucleus, and is categorically stiffer compared to a softer viscoelastic cytoplasm with large compliance. Remarkably, subsequent observations reveal that a secondary nuclear stress relaxation regime emerges in response to mechanical failure of the vimentin cage at rapidly elevated stress. These observations provoke fundamental biophysical questions in our understanding of nuclear and cellular mechanics. In this work we explore the role of vimentin in giving rise to distinct nuclear mechanics which previous studies reported can be up to an order of magnitude stiffer than the cytoplasm. We further probe the forces that that bind vimentin cage to the nucleoskeleton. Furthermore, we investigate how an interconnected biopolymeric network remodel to disentangle in response to stress induced by micropipette aspiration. Finally, we highlight the implications of the vimentin nuclear cage in chromatin organization and associated genetic conditions such as progeria.