NOV 13, 2018 4:01 PM PST

The Mechanism of a Cell-penetrating Peptide is Revealed

WRITTEN BY: Carmen Leitch

Cells have a barrier around them, which carefully controls what can move across it. There a variety of different ways for things to traverse that cell membrane, and scientists have now discovered a new one. The findings may have significant implications for drug design - transporting therapeutics into cells is a major goal in pharmaceutical development. The study, led by Pavel Jungwirth from the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague), has been reported in the Proceedings of the National Academy of Sciences (PNAS). 

Electron microscopy image of a bifurcating cell membrane and the corresponding molecular scheme of the process. / Credit: @ IOCB Prague

A few decades ago, it was found that some short peptides (chains of amino acids) were able to get across the cell membrane. Researchers have used that finding in drug development, as a way to move therapeutics into the cell. However, not much is known about how that works.  

Generally, getting stuff into the cells means relying on a process called vesicular transport, in which a vesicle can bud from the membrane and envelope a particle that’s then moved into the cell. If that particle happens to be a drug, it must then be able to get out of the vesicle; otherwise, it can interfere with drug efficacy. 

In this work, researchers focused on peptides, to see how they were moving across the cell membrane. With a combination of tools, including electron microscopy, fluorescence, and computer modeling, the team revealed how positively-charged peptides can enter cells without using energy - passively. The peptides do not pass through the membrane - a lipid bilayer - directly. Instead, they use vesicles by stimulating a kind of membrane fusion. The researchers were able to visualize that process in action.

Membrane fusion is a well-known cellular mechanism. The name basically describes the process, in which two different lipid membranes come together to form one. Cell membrane bifurcation can be seen in the video above, while cell membrane fusion is illustrated in the following video.

"At this point, we can only speculate as to practical applications for the discovery," conceded Pavel Jungwirth. "If, however, this newly discovered mechanism proves sufficiently robust, in the future we could consider the possibility of passively transporting drug molecules into cells without having to free them from vesicles, which in this process simply don't form."

Jungwirth leads a team that focuses on studying the molecular mechanisms used by the cell, many of which are still not well-described. Understanding basic biology is essential if we are going to control the processes when they go awry, and therapeutics have to be applied.

 

Sources: AAAS/Eurekalert! via IOCB Prague, PNAS

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
DEC 18, 2019
Genetics & Genomics
DEC 18, 2019
Learning More About The Genetic Adaptations Cancer Relies On
Cancer cells can adapt to mutations in the genome that might kill the cells by altering the activity of their genes....
JAN 16, 2020
Cell & Molecular Biology
JAN 16, 2020
Understanding the Restorative Power of Sleep
Scientists have learned more about how sleep gets us ready to face the challenges of the day....
JAN 26, 2020
Cell & Molecular Biology
JAN 26, 2020
Using Stem Cells to Treat Chronic Pain
Scientists have used a mouse model to show that human stem cells could be used to engineer neurons that stop pain....
FEB 09, 2020
Cell & Molecular Biology
FEB 09, 2020
Switching Inflammation Off at the Molecular Level
While chronic inflammation is a natural result of getting old, experiencing stress, and toxin exposure, it's been theorized to be the basis for many chronic diseases....
FEB 10, 2020
Cell & Molecular Biology
FEB 10, 2020
Lighting a Path to an Alzheimer's Disease Treatment
Alzheimer's impacts millions of people around the world; globally, it is thought to cost $605 billion a year, and there is still no way to treat it....
FEB 09, 2020
Cell & Molecular Biology
FEB 09, 2020
Learning More About X Chromosome Inactivation
The X chromosome carries a thousand genes, so in females, one of the X chromosomes must be silenced to avoid serious developmental consequences....
Loading Comments...