Researchers at BGU have successfully replicated under laboratory conditions the interaction between lymphocytes and “sick" cells, and have quantified the mechanism by which lymphocytes distinguish between sick cells and healthy ones.
In a groundbreaking paper published in the peer-reviewed Advanced Materials journal, the team headed by Dr. Mark Schvartzman of the Department of Materials Engineering and Prof. Angel Porgador of the Shraga Segal Department of Microbiology, Immunology and Genetics, show that by introducing lymphocytes to an artificially-created laboratory “skin of target cells" in the form of a dense array of nanowires – vertical nanostructures with the diameter of a few tens of nanometers - they were able to observe the lymphocytes' mechanical, as well as chemical, reaction to the cells.
The team, which also included Netanel Bar-Hanin, Dr. Guillaume Le Saux, Dr. Uzi Hadad, and Avishay Edri, developed a unique chemical method to coat the nanowires with antigen molecules – specific markers on the surface of ill cells - thus making the artificial cell skin chemically identical to that of real ill cells. They introduced the lymphocytes to the artificial cells and found that the lymphocytes grabbed the nanowires and bent them towards the middle of the cell.
Surprisingly, the researchers found that upon bending of the nanowires, the cells secreted large amounts of a toxic material they use for killing viral and tumorous cells in human body.
“We have known for a long time that lymphocytes use chemical excretions to identify and kill 'enemy' cells inside the body, but this was the first time we were able to observe the mechanical process that occurs at the same time," said Dr. Schvartzman, the lead author. “Observing this process has been impossible, mostly due to the difficulty in reproducing the mechanical features of probed cells, whose surface is landscaped with complex nanometric shapes, under lab conditions.
“Also, the force applied by lymphocytes on the target cell is extremely small, and are often scaled in units of picoNewton, or one- one trillionth (1/100,000,000,000,000) of a Newton. So detecting and measuring the level of force exerted by the lymphocyte on the target cell has been extremely challenging," Schvartzman added.
The discovery of the mechanism by which lymphocytes recognize ill cells is an important step for immunotherapy research, which has been a focus of cancer treatment research in recent years. Today's vision is to expand immunotherapy, which could be more effective and safer than chemotherapy, against all types of cancer, and make it personalized.
But to date, progress has been hampered by the inability to understand the mechanism by which lymphocytes recognize ill cells, such as tumors.
“We still have barely scratched the surface of our knowledge of the human immune system. But the discovery of this mechanism is an important step and will serve as a springboard for further research that will expand our basic understanding that is necessary for the development of future immunotherapies," Dr. Schvartzman said.
Above: a) Schematic drawing of NK activation on MICA‐functionalized nanowires. b) SEM of NK cells on MICA‐functionalized nanowires.
