Nuclear pores as conduits for fluid flow during osmotic stress

Abstract

Changing environmental conditions necessitate an immediate cellular adaptation to ensure survival.Dictyostelium discoideum, a bacteriovore slime mold present in the soil of most terrestrial ecosystems, is known for its ability to tolerate drastic changes in osmolarity. How the cells cope with the resulting mechanical stress remains understudied. Here we show thatD. discoideumhas extraordinarily elaborate and resilient nuclear pores that serve as conduits for massive fluid exchange between cytosol and nucleus. We capitalize on the unique properties ofD. discoideumcells to quantify flow across the nuclear envelope that is necessitated by changing nuclear size in response to osmotic stress. Based on mathematical concepts adapted from hydrodynamics, we conceptualize this phenomenon as porous flow across nuclear pores. This type of fluid flow is distinct from the canonically characterized modes of nucleocytoplasmic transport, i.e. passive diffusion and active nuclear transport, because of its dependence on pressure. Our insights are relevant in any biological condition that necessitates rapid nuclear size changes, which includes metastasizing cancer cells squeezing through constrictions, migrating cells and differentiating tissues.

Passage of the HIV capsid cracks the nuclear pore

“…That the HIV-1 capsid cracks the NPC was not necessarily intuitive, because the NPC scaffold is an elaborate structure designed to persist strain laterally imposed by the nuclear membranes 25,43,47 , while the capsid has to disintegrate at some stage during the post-entry process. The exact forces remain challenging to measure experimentally.…”