How do peptides penetrate cells? Two sides of the same corner

The simple transport of drugs is one of the primary goals of the pharmaceutical industry. In large part, researchers still do not possess a detailed understanding of the molecular level of the processes responsible for transporting substances into and out of cells. In collaboration with colleagues from the Czech Republic and Germany, the research team of the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague) has discovered and in principle, could serve as the carriers of drug molecules. The results of their research Proceedings of the National Academy of Sciences .

The ability of positively charged peptides to penetrate cells was first observed in HIV research, and today. Until now, however, this is essentially a form of transport, ie, by means of a transport vesicle separating from the cell membrane and enveloping the transported substance. complete, potentially posing a technical complication for the efficient transportation of the drug. It is known that peptides can also penetrate cells pbadively, independently of energy from the cell, but the exact mechanism has yet to be described.

Now, using fluorescence and electron microscopy in combination with molecular computer simulations, the scientists have discovered a previously validated pbadive mechanism for positively transferring peptides into cells. It is based on membrane fusion induced by the transported peptides (see the image). The scientists have thus demonstrated that the process of pbadive transport of peptides into the known fusion process for membrane fusion, which is induced by calcium ions in neurons during the transmission of nerve impulses-share the same mechanistic basis. Figuratively speaking, they're two sides of the same coin.

"At this point, we can only speculate as to practical applications for discovery," says Jungwirth. "If, however, this newly discovered mechanism is robust enough, in the future, we could consider the possibility of pbadively transporting drug molecules into cells, which, in this process, simply do not form."

Jungwirth and his team have long focused on revealing the laws governing molecular processes in the cell membrane, which, to this day, are still largely unknown. A better understanding of the basic processes is possible within the framework of the methods of transporting drugs to their sites of action.

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More information:
Christoph Allolio et al., Arginine-rich cell-penetrating peptides induce multilamilarity membrane and subsequently enter via formation of a fusion pore, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073 / pnas.1811520115