Multispecies transport shapes electrochemical environments in perforated cells

Gasdermin-perforated cells exhibit non-canonical Donnan-like electrochemical states driven by ion–protein transport timescale separation, with pore clustering and sequential pore formation shaping osmotic gradients and dynamics.

• Why it matters: Phenotypic progression from pore formation to cell swelling has been observed for decades, but the molecular transport events linking these stages are unclear.
• What they did: The authors built quantitative multispecies transport frameworks, benchmarked a reductionist model against analytical Donnan predictions, and simulated 3D geometries with individual pores or pore clusters forming simultaneously or sequentially.
• The result: They find that cargo and pore properties tune local transport, clustering modulates osmotic gradients, and sequential pore formation yields feedback-dependent dynamics, informing mechanistic understanding and therapeutic design of tunable pore-forming proteins.

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