Reversible permeabilization of plasma membranes with an engineered switchable pore

• Published in: Nature biotechnology Vol. 15; no. 3; pp. 278 - 282
• Main Authors: RUSSO, M. J, BAYLEY, H, TONER, M
• Format: Journal Article
• Language: English
• Published: New York, NY Nature 01.03.1997
• Subjects: 3T3 Cells; Animals; Bacterial Toxins - genetics; Bacterial Toxins - pharmacology; Biological and medical sciences; Biological Transport; Cell Membrane Permeability - drug effects; Diverse techniques; Fibroblasts - cytology; Fibroblasts - metabolism; Fibroblasts - ultrastructure; Fundamental and applied biological sciences. Psychology; Hemolysin Proteins - genetics; Hemolysin Proteins - pharmacology; Mice; Microscopy, Electron; Molecular and cellular biology; Mutagenesis; Sucrose - metabolism; Zinc - pharmacology; Sucrose; Rodentia; 3T3-Cell line; Permeabilizing; Metal; Toxin; Vertebrata; Mammalia; Mouse; Plasma membrane; Membrane pore; Reversibility; Technique; Fibroblast
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt0397-278

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 (approximately 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 microM 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.