Wasp Venom Peptide Selectively Punctures Cancer Cell Membranes

Though few people would welcome a sting from the Brazilian wasp Polybia paulista, the wasp’s venom does contain a potentially useful molecule. The venom peptide MP1 selectively kills human cancer cells by creating pores in their membranes. Now researchers have found out why MP1 attacks tumor cells but not healthy ones.

The explanation suggests a possible new cellular structure to target when designing cancer drugs.

Research teams at São Paulo State University in Brazil and the University of Leeds in England determined that MP1’s selectivity arises from differences in the compositions of the phospholipid bilayers that make up healthy and cancer cell membranes (Biophys. J. 2015, DOI: 10.1016/j.bpj.2015.07.033). Tumor endothelial cells have large numbers of phospholipids called phosphatidylserine (PS) and phosphatidylethanolamine (PE) in the outer layer of their membranes; healthy cells do not.

To test whether MP1 targets this difference, the research groups created model membrane layers in solution composed of different combinations of phospholipids: one with just a common phospholipid called phosphatidylcholine (PC), one with PS and PC, one with PE and PC, and one with all three.

Using several types of imaging, including atomic force microscopy, researchers found that MP1 didn’t form pores in the PC-only membranes. The peptide bound to the PC/PS membrane, but the pores it made were small enough for the membrane to seal itself. The PC/PE membrane, on the other hand, created larger pores but in small quantities. Only with the PC/PE/PS membrane did MP1 produce pores numerous enough and severe enough to create leaks able to kill a cell.

The prevailing wisdom in drug development is that membrane lipids aren’t good drug targets because drug interactions with them are not specific, says Georg Pabst, professor of molecular biosciences at the University of Graz in Austria. “The present study nicely shows that interactions with membrane lipids are specific indeed.” Pabst, who was not involved in the study, says the researchers’ results “strongly nurture a change in paradigm in drug design.”