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an RBC; Credit: St Jude
Children’s Research Hospital
Researchers say laser optical tweezers have allowed them to study how Plasmodium falciparum interacts with red blood cells (RBCs) at the single-cell level.
The research has revealed new insights into malaria biology and may pave the way for more effective drugs or vaccines.
Julian Rayner, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK, and his colleagues described their use of laser optical tweezers in Biophysical Journal.
“Using laser tweezers to study red blood cell invasion gives us an unprecedented level of control over the whole process and will help us to understand this critical process at a level of detail that has not been possible before,” Dr Rayner said.
He and his colleagues noted that P falciparum merozoites usually leave one RBC and invade another in less than a minute. And the merozoites lose the ability to infect host cells within 2 or 3 minutes of release.
So the researchers used laser optical tweezers to study this transient event. The tweezers allow for precise control over the movements of cells by exerting extremely small forces with a highly focused laser beam.
The team used the tweezers to pick up individual merozoites that had just emerged from an RBC and deliver them to another RBC, demonstrating that the technique is suitable for studying the invasion process.
The researchers also used the tweezers to measure how strongly the merozoites adhere to RBCs. They discovered that attachment is probably mediated by multiple weak interactions, which could potentially be blocked by a combination of drugs or antibodies.
Finally, the team used the tweezers to shed light on how 3 different invasion-inhibiting drugs—heparin, cytochalasin D, and chymotrypsin—affect interactions between merozoites and RBCs.
The tweezers revealed that heparin blocks merozoite attachment to any surface, including glass slides. This suggests a receptor-independent mode of action, which contradicts the previously proposed mechanism.
Cytochalasin D, on the other hand, had no effect on attachment force, a finding that also contradicts previous thought.
And with chymotrypsin, the researchers observed 2 different effects. When merozoites adhered to chymotrypsin-treated RBCs, they did so with a reduction in the force of attachment that was similar to the effect the enzyme had on the overall efficiency of invasion.
However, merozoites that had been released more than 3 minutes previously were no longer able to adhere to chymotrypsin-treated RBCs. This suggests that chymotrypsin affects both the force of merozoite attachment and the time in which invasion can occur.
Taken together, these findings show that optical tweezers enable the study of malaria biology and drug mechanisms at the single-cell level.
“We now plan to apply this technology to dissect the process of invasion and understand what genes and proteins function at what step,” Dr Rayner said. “This will allow us to design better inhibitors or vaccines that block invasion by targeting multiple steps at the same time.” 
an RBC; Credit: St Jude
Children’s Research Hospital
Researchers say laser optical tweezers have allowed them to study how Plasmodium falciparum interacts with red blood cells (RBCs) at the single-cell level.
The research has revealed new insights into malaria biology and may pave the way for more effective drugs or vaccines.
Julian Rayner, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK, and his colleagues described their use of laser optical tweezers in Biophysical Journal.
“Using laser tweezers to study red blood cell invasion gives us an unprecedented level of control over the whole process and will help us to understand this critical process at a level of detail that has not been possible before,” Dr Rayner said.
He and his colleagues noted that P falciparum merozoites usually leave one RBC and invade another in less than a minute. And the merozoites lose the ability to infect host cells within 2 or 3 minutes of release.
So the researchers used laser optical tweezers to study this transient event. The tweezers allow for precise control over the movements of cells by exerting extremely small forces with a highly focused laser beam.
The team used the tweezers to pick up individual merozoites that had just emerged from an RBC and deliver them to another RBC, demonstrating that the technique is suitable for studying the invasion process.
The researchers also used the tweezers to measure how strongly the merozoites adhere to RBCs. They discovered that attachment is probably mediated by multiple weak interactions, which could potentially be blocked by a combination of drugs or antibodies.
Finally, the team used the tweezers to shed light on how 3 different invasion-inhibiting drugs—heparin, cytochalasin D, and chymotrypsin—affect interactions between merozoites and RBCs.
The tweezers revealed that heparin blocks merozoite attachment to any surface, including glass slides. This suggests a receptor-independent mode of action, which contradicts the previously proposed mechanism.
Cytochalasin D, on the other hand, had no effect on attachment force, a finding that also contradicts previous thought.
And with chymotrypsin, the researchers observed 2 different effects. When merozoites adhered to chymotrypsin-treated RBCs, they did so with a reduction in the force of attachment that was similar to the effect the enzyme had on the overall efficiency of invasion.
However, merozoites that had been released more than 3 minutes previously were no longer able to adhere to chymotrypsin-treated RBCs. This suggests that chymotrypsin affects both the force of merozoite attachment and the time in which invasion can occur.
Taken together, these findings show that optical tweezers enable the study of malaria biology and drug mechanisms at the single-cell level.
“We now plan to apply this technology to dissect the process of invasion and understand what genes and proteins function at what step,” Dr Rayner said. “This will allow us to design better inhibitors or vaccines that block invasion by targeting multiple steps at the same time.”
an RBC; Credit: St Jude
Children’s Research Hospital
Researchers say laser optical tweezers have allowed them to study how Plasmodium falciparum interacts with red blood cells (RBCs) at the single-cell level.
The research has revealed new insights into malaria biology and may pave the way for more effective drugs or vaccines.
Julian Rayner, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK, and his colleagues described their use of laser optical tweezers in Biophysical Journal.
“Using laser tweezers to study red blood cell invasion gives us an unprecedented level of control over the whole process and will help us to understand this critical process at a level of detail that has not been possible before,” Dr Rayner said.
He and his colleagues noted that P falciparum merozoites usually leave one RBC and invade another in less than a minute. And the merozoites lose the ability to infect host cells within 2 or 3 minutes of release.
So the researchers used laser optical tweezers to study this transient event. The tweezers allow for precise control over the movements of cells by exerting extremely small forces with a highly focused laser beam.
The team used the tweezers to pick up individual merozoites that had just emerged from an RBC and deliver them to another RBC, demonstrating that the technique is suitable for studying the invasion process.
The researchers also used the tweezers to measure how strongly the merozoites adhere to RBCs. They discovered that attachment is probably mediated by multiple weak interactions, which could potentially be blocked by a combination of drugs or antibodies.
Finally, the team used the tweezers to shed light on how 3 different invasion-inhibiting drugs—heparin, cytochalasin D, and chymotrypsin—affect interactions between merozoites and RBCs.
The tweezers revealed that heparin blocks merozoite attachment to any surface, including glass slides. This suggests a receptor-independent mode of action, which contradicts the previously proposed mechanism.
Cytochalasin D, on the other hand, had no effect on attachment force, a finding that also contradicts previous thought.
And with chymotrypsin, the researchers observed 2 different effects. When merozoites adhered to chymotrypsin-treated RBCs, they did so with a reduction in the force of attachment that was similar to the effect the enzyme had on the overall efficiency of invasion.
However, merozoites that had been released more than 3 minutes previously were no longer able to adhere to chymotrypsin-treated RBCs. This suggests that chymotrypsin affects both the force of merozoite attachment and the time in which invasion can occur.
Taken together, these findings show that optical tweezers enable the study of malaria biology and drug mechanisms at the single-cell level.
“We now plan to apply this technology to dissect the process of invasion and understand what genes and proteins function at what step,” Dr Rayner said. “This will allow us to design better inhibitors or vaccines that block invasion by targeting multiple steps at the same time.”