A computer generated video of a cell membrane being “pierced” by HIV peptides
The positively charged HIV peptides (shown in red) are drawn to negatively charged phosphates (shown in yellow) in the cell membrane. When an HIV peptide cannot satisfy itself with the negative charges available on the cell membrane surface it is directly attached to, it reaches through the membrane to grab negatively charged phosphates (shown in green) on the other side, opening a hole in the cell. Once all the peptides have been neutralized, the reaction stops and the hole closes, leaving behind a healthy, viable cell.
Observations and Results
As was expected, in their simulations the researchers observed that the positive charges in the peptide quickly attached to the surface of the cell membrane and sought out and reacted with negatively charged phosphates from the charged portion of the lipid bilayer to satisfy their need for neutrality. “Then the peptide entered the forbidden territory of the cell,” Garcia said. The positively charged peptide entered the membrane. “This is when this mechanism starts to challenge conventional wisdom,” he said.
The researchers’ model systems show the peptides grabbing for surrounding negative charges, but when no more of those charges are available due to their greedy peptide neighbors, some of the peptides reach into the cell membrane and grab negative charged phosphates from the other side. This opens a hole in the cell membrane and allows the flow of water and other material into the cell. Once all the peptides have been neutralized, the reaction stops and the hole closes, leaving behind a healthy, viable cell.
For the paper, the researchers reported a dozen different simulations run through a high-powered cluster of computers. Each simulation required a long process of testing and validating results. Garcia’s computer cluster is now running simulations on the use of antimicrobial proteins which will open a pore in the cell and keep it open, killing the cell. Antimicrobial proteins have promising direct applications for killing harmful cells in the body.
Garcia hopes to harness the power of Rensselaer’s newly opened Computational Center for Nanotechnology Innovations (CCNI), which houses the world’s most powerful university-based supercomputing center. The CCNI will allow him to compile two years’ worth of data on his normal cluster in just 10 to 20 days.
The research was funded by the National Science Foundation (NSF) through the Rensselaer Nanoscale Science and Engineering Center for Directed Assembly of Nanostructures (NSEC) and Rensselaer Polytechnic Institute. Garcia is a member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies.