Reversible permeabilization of plasma membranes with an engineered switchable pore

By using an engineered, self-assembling, proteinaceous, 2-nm pore equipped with a metal-actuated switch, a technique to reversibly permeabilize the plasma membrane to small molecules (∼1000 Da) has been developed. We have demonstrated the dose-dependent permeabilization of fibroblasts by pores designed to be blocked and unblocked by the addition and removal of μM concentrations of Zn2+. Further, we have shown that the activity of the switch allows permeabilized cells to maintain viability and ultrastructural integrity following the unconstrained flux of small molecules. This ability to control the transmembrane influx and efflux of molecules and thereby vary the intracellular environment yet maintain cell viability will impact an array of biological and medical problems.