Researchers can finally control the viscosity of cell membranes

Cell membranes are the basis for all life, including humans, animals, plants and microorganisms. No cells could exist without cell membranes. Cell membranes confine the cell’s DNA, prevent the nucleus from dissipating into the surroundings and exchange numerous molecules between the cell and its environment. This is equivalent to a Swiss army knife in biology.

Cell membranes comprise lipids (fat), wax, sterols (steroid alcohols), fat-soluble vitamins and much more. Researchers have now discovered how to very precisely manipulate cell membranes and control their viscosity, meaning how fluid and flexible the cell membranes are (low viscosity means more fluid). This discovery is revolutionary and paves the way for manipulating completely new forms of microorganisms with new properties and understanding various diseases.

“We now have many new opportunities to manipulate cell membranes and can study them more closely and, for example, make microorganisms more resistant to heat, cold or pressure. This has far-reaching perspectives in such fields as medicine and biochemical synthesis,” explains the lead researcher of the new study, Jay D. Keasling, Professor of Chemical Engineering and Bioengineering and Principal Investigator, Keasling Lab, University of California, Berkeley and Lawrence Berkeley National Laboratory; and Scientific Director, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark.

The study has been published in Science.

Cell membranes are dynamic

Although cell membranes may appear relatively static to the naked eye or under a microscope, they are not. Cell membranes are very dynamic, and their viscosity changes continually.

For example, when a cell needs to grow, the cell membrane must become very fluid so it can stretch and expand. When the cell environment is hot, the cell membranes must not be too fluid otherwise their whole structure collapses – similar to butter melting on a hot day. Conversely, cell membranes must not be too viscous when the cell environment is cold, because this makes the cells fragile.

Cell membranes have genetic and molecular tools that enable them to constantly adjust the composition of fatty acids in the membrane to control their viscosity. Unsaturated fatty acids make cell membranes more fluid, and saturated fatty acids make them more viscous. The ratio between the two types of fatty acids determines the viscosity.

Jay D. Keasling and his colleagues have discovered how to control this ratio between saturated and unsaturated fatty acids.

“Over the years, we have developed various molecular tools that enable us to very precisely control the ratio between saturated and unsaturated fatty acids in cell membranes. This means that, for example, we can now control whether a cell is able to grow and how much energy can pass through a membrane,” explains Jay D. Keasling.

Manipulating E. coli bacteria to produce more unsaturated fatty acids

The tools the researchers use mostly comprise promoters that control the expression of genes that encode enzymes to produce each type of fatty acid. In their study, the researchers initially manipulated the genes of Escherichia coli bacteria and yeast cells to produce unsaturated fatty acids through an L-arabinose promoter. When the researchers gave the E. coli L-arabinose, a simple sugar, the bacteria increased their production of unsaturated fatty acids.

The researchers could thereby continually control the ratio between saturated and unsaturated fatty acids in the cell membranes of the E. coli. This is just one of the tools the researchers use.

“In the system we constructed, L-arabinose activates or stops the production of unsaturated fatty acids, like a light switch that is either on or off. In this analogy, we created a dimmer switch enabling us to make the light brighter or dimmer,” says Jay D. Keasling.

Greater insight into diseases

Since the researchers can now control the viscosity of cell membranes, they will use the tools to both study and manipulate.

First, various diseases can be associated with changes in the viscosity of cell membranes. One such disease is diabetes; many researchers believe that a high-fat diet changes the composition of fatty acids in the cell membranes and thereby changes glucose uptake, insulin signalling and other factors. Huntington’s disease is another disease researchers associate with changes in the viscosity of cell membranes.

The ability to manipulate the viscosity of cell membranes means that the researchers can more easily study how changes in viscosity may be associated with the development of various diseases.

This also applies to other major noncommunicable diseases.

“Cell membranes contain cholesterol, and manipulating cell membranes will enable us to study how we might be able to influence the high cholesterol levels that affect many people,” says Jay D. Keasling.

Producing bacteria for the chemical industry

Second, the researchers can also begin to manipulate new properties into microorganisms.

One way is to change the viscosity of cell membranes to design microorganisms resistant to cold, heat or pressure.

Many companies use biochemical synthesis to make everything from chemicals to medicine. One problem is that the cells they want to use in the synthesis – often E. coli – cannot tolerate the optimal temperature or pressure for producing the desired substances.

“Our discovery brings us much closer to being able to produce cells that are custom-designed for chemical synthesis. We can also imagine creating membranes of a specific viscosity that can purify water. This discovery has many far-reaching perspectives,” concludes Jay D. Keasling.

“Viscous control of cellular respiration by membrane lipid composition” has been published in Science. Jay D. Keasling is Professor of Chemical Engineering and Bioengineering and Principal Investigator, Keasling Lab, University of California, Berkeley and Lawrence Berkeley National Laboratory; and Scientific Director, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark.