Pulling a protein complex apart has allowed US scientists to unravel some of the secrets of membrane fusion. 

Membrane fusion is an important biological event involved in a range of cellular processes including egg fertilisation by sperm and waste transport. It is also the mechanism by which some pathogens enter cells. Now, Vincent Moy from the University of Miami, Florida, US, and colleagues have used atomic force microscopy (AFM) to measure the force required to pull apart SNARE complexes, protein complexes involved in the membrane fusion process.

A SNARE complex resembles a rope linking two cell membranes, pulling them together

When membranes fuse, SNARE proteins from different membranes combine to form a complex that helps pull the membranes together. SNARE complex formation 'exerts a mechanical force which is transmitted to the membranes, bringing them together and disrupting them,' explains Midhat Abdulreda, who worked on the AFM project. The membranes' hydrophobic nature ensures that the disrupted membranes then fuse together.  

The US team's approach assumes that the unbinding process as the SNARE complex is pulled apart is the reverse of the binding process, effectively allowing the researchers to monitor SNARE complex formation - in reverse. 

Using the AFM approach, Moy's team showed that the pulling force exerted on the membranes by the SNARE complex facilitates membrane hemifusion - where only the outer membranes are mixed and the inner membrane remains intact - and that it also increases the likelihood of complete membrane fusion. 

The researchers were also able to show for the first time that there is a direct correlation between the strength of the SNARE interaction and SNARE-mediated membrane fusion. Further studies of the complexes revealed that two energetically different steps govern SNARE complex formation. 'There are two force loading regimes, indicating the presence of two activation barriers in the dissociation of the SNARE complex,' explains Devrim Pesen Okvur, an expert in applied biophyics at Yeshiva University, New York, US.

Tanya Dahms, an expert in physical biochemistry, at the University of Regina, Saskatchewan, Canada, welcomes the research. The experimental system is well-designed, says Dahms, and the group has used this in a powerful combination with AFM spectroscopy to understand biological processes at the molecular level, she adds.  

Russell Johnson

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