Unravelling cell membranes to understand drugs

Researchers in Sweden have found a way to create flattened cell membranes, known as supported lipid bilayers, out of real cell structures. Their technique could help improve understanding of cell membranes and their interactions with drugs or viruses. 

Supported lipid bilayers are important tools for researchers who want to investigate the properties of cell membranes. Scientists create these bilayers by putting lipid vesicles in solution above a solid support. At a critical coverage the vesicles burst and fuse producing a two-dimensional membrane that can be studied with a microscope or other surface-based techniques. 

But, while real cell membranes are made up of hundreds of different lipids as well as proteins, most supported lipid bilayers are very simple. ’Only a few lipids rupture spontaneously,’ says author Lisa Simonsson of Chalmers University of Technology, Sweden. ’That’s a problem because what we really want to investigate are more complex systems which are more like a real cell membranes.’ 

To make more complex structures, Simonsson and her colleagues turned to microfluidics. They placed a supported lipid bilayer at the bottom of a buffer-filled channel 100?m in width and height. By syringing more buffer into one end of the channel, the team were able to move the bilayer towards a set of lipid vesicles also in solution. They found that when the edge of the lipid bilayer reached the vesicles they ruptured and flattened. 

’What we saw happen was those vesicles were actually incorporated into the moving supported lipid bilayer,’ says Simonsson. ’So therefore we realised we could transfer vesicles which would not spontaneously form a supported lipid bilayer into one.’   

The team successfully tested their technique with artificial vesicles, as well as vesicles made from real cell membranes. Using the approach they were also able incorporate additional structures such as cell membrane proteins. 

’Rolling real cell membranes out on a solid support for analysis of their native protein content is a big step forward,’ says Joachim R?dler, who studies supported membranes at the Ludwig Maximilians University Munich, Germany. Being able to study complex cell membrane structures is interesting from many points of view - not least investigating their interactions with drugs or viruses. 

The method also allowed Simonsson to manipulate the incorporated components within the bilayer. For example, the team could move proteins that protruded into solution around the two-dimensional structure, using the buffer flow. The bilayer acts as a chromatograph - the proteins move at different speeds depending on their size. 

’This is extremely nice work demonstrating a novel method for incorporation of cell membrane content into supported lipid bilayers,’ says Paul Cremer, a professor at the Texas A&M University, US. ’Such work should help show the way for screening and separating components from native membranes.’   

’What we want to do now is study membrane spanning proteins,’ adds Simonsson. ’There’s still a lot of research to do - we’ve just opened the door.’ 

Manisha Lalloo