New insight into cell membranes could improve drug testing and design

January 22, 2019 by Camilla Shumaker, University of Arkansas
This image illustrates researchers' findings that the membrane proteins can be active, contributing to drug resistance, in cell membranes with one type of lipid composition (top), but inactive in membranes with a different lipid composition (bottom). Credit: Mahmoud Moradi

Research at the University of Arkansas on membrane proteins could lead to better development and testing of drugs. Chemistry researchers studied a type of membrane protein that expels drugs from a cell, contributing to drug resistance. They found that the lipid composition of the cell membrane has an effect on the behavior of these proteins, which should be taken into account when testing drugs that target membrane proteins. Their results are available open-access in the journal ACS Central Science.

Drug resistance, including bacterial resistance to antibiotics and cancer cells' resistance to chemotherapy, is a significant challenge for drug developers.

"Almost two-thirds of all drugs target ," explained Mahmoud Moradi, assistant professor of chemistry and biochemistry. "This research looks at how membrane proteins interact with the environment. If you ignore the fact that these proteins are dependent on their environment, you could end up with the wrong drugs."

Moradi and colleagues studied a type of membrane called multi-drug ABC exporters. These proteins transport substances, such as drugs, from the inside to the outside of cells, and they are responsible for both antibiotic resistance in bacteria and chemotherapy resistance in .

Using specially designed supercomputers supported by the National Science Foundation and the National Institutes of Health, the researchers performed molecular simulations to investigate how the lipid composition of a cell's membrane affects these proteins.

They found that these proteins remained inactive and didn't expel drugs in cell membranes with one type of lipid composition, called phosphocholine, or PC. However, the same proteins became active in cells with a different lipid composition, called phosphoethanolamine, or PE, allowing them to release drugs and making the cell resistant. Among the cell membranes composed of PE lipids, those containing one particular lipid type, called POPE, proved to be most effective in activating these proteins and thus most susceptible to . Taking this information about the lipid environment into account could help researchers more effectively develop and test antibiotics and cancer treatments.

Explore further: New research looks at novel ways to combat drug resistance

More information: Kalyan Immadisetty et al. Lipid-Dependent Alternating Access Mechanism of a Bacterial Multidrug ABC Exporter, ACS Central Science (2019). DOI: 10.1021/acscentsci.8b00480

Related Stories

Testing cells for cancer drug resistance

October 26, 2018

Biophysicists at Ruhr-Universität Bochum (RUB) have demonstrated that Raman microscopy can be used to detect the resistance of tumour cells to cancer drugs. Unlike conventional approaches, this method does not require any ...

Recommended for you

Archaeologists discover Incan tomb in Peru

February 16, 2019

Peruvian archaeologists discovered an Incan tomb in the north of the country where an elite member of the pre-Columbian empire was buried, one of the investigators announced Friday.

What rising seas mean for local economies

February 15, 2019

Impacts from climate change are not always easy to see. But for many local businesses in coastal communities across the United States, the evidence is right outside their doors—or in their parking lots.

The friendly extortioner takes it all

February 15, 2019

Cooperating with other people makes many things easier. However, competition is also a characteristic aspect of our society. In their struggle for contracts and positions, people have to be more successful than their competitors ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.