Rice, Brookhaven physicists decode initial stage of cell fusion

n Yang, a former graduate student of Huang at Rice and now a postdoctoral physicist at Brookhaven's National Synchrotron Light Source (NSLS), used a variant of X-ray crystallography called X-ray diffraction to experimentally confirm a longstanding theory about the initial bridge that forms between membranes. Understanding the basic structure of this initial molecular connection is critical for isolating the energy barriers that fusion proteins need to overcome in order to initiate cell fusion.

To reveal the structure of the fused cell membranes, Huang and Yang first produced small crystals composed of stacks of membranes made of phospholipids. Then, they projected x-rays produced by the NSLS toward the crystals. By looking at how the x-rays scattered off the crystals, Huang and Yang were able to create diffraction patterns, maps of the atomic structure of the phospholipid layers in the membranes.

By dehydrating a stack of membranes, the scientists were able to induce membrane fusion. Analysis of the diffraction patterns of these samples confirmed that the two membranes were caught in the act of fusing. These diffraction patterns showed that membrane fusion begins with the formation of an hourglass-shaped structure called a stalk, which theorists had predicted.

"Now that we know what the structure is, we can calculate the free energy pathway -- which is a sort of map that will show where the energy barrier is for membrane fusion," said Huang. "Ultimately, medical researchers working on gene therapy and drug delivery would like to find out how two membranes fuse, because they'd like to be able to activate the fusion process in order to deliver new genes and drugs to patients. Currently, fusion is the bottleneck to non-viral gene delivery."


Contact: Jade Boyd
Rice University

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