Multispecies transport shapes electrochemical environments in perforated cells

Cells sustain distinct electrochemical environments across selectively permeable plasma membranes. Ion channels in these membranes facilitate the movement of small ions, while larger openings, such as gasdermin pores, permit both ions and proteins to pass through. This multispecies transport system drives changes in osmolarity, which in turn causes water to enter the cell and lead to swelling.

While biologists have documented the progression from pore formation to cell swelling for many years, the molecular processes behind this phenomenon have remained unclear. Researchers have developed quantitative models to explore how pore formation leads to downstream cellular effects.

To better understand this process, scientists have established a reductionist model and compared it to analytical Donnan predictions. They have examined both individual pores and clusters of pores that form either simultaneously or sequentially. Their findings reveal that the separation of ion and protein timescales gives rise to non-canonical Donnan-like states.

The properties of the pore and cargo also influence local transport, while clustering pores modulate osmotic gradients. Moreover, sequential pore formation can produce feedback-dependent dynamics.

This research enhances our understanding of the molecular mechanisms behind cellular responses to membrane damage and provides insights into designing pore-forming proteins with controllable cellular effects for therapeutic purposes.