Led by University of Illinois electrical and computer engineering professor Gabriel Popescu, the team developed a model that could lead to breakthroughs in screening and treatment of blood-cell-morphology diseases, such as malaria and sickle-cell disease. The group published its findings in the Proceedings of the National Academy of Sciences.
Red blood cells (RBCs) are unique in structure – a doughnut-shaped disc full of the oxygen-carrying molecule hemoglobin but none of the intracellular structures of other cells, not even DNA. In circulation, RBCs must contort to squeeze through capillaries half their diameter. Their flexibility and resilience come from their membrane structure, which couples a typical lipid bilayer with an underlying matrix of protein. However, knowledge of the membrane’s mechanics is very limited.
“The deformability of red blood cells is their most important property,” said Popescu, also affiliated with the Beckman Institute for Advanced Science and Technology at U. of I. “What we wanted to find is, how does deformability relate to morphology?”
The research team used a novel measurement technique called diffraction phase microscopy, which uses two beams of light while other microscopes only use one.
“One beam goes through the specimen and one beam is used as a reference,” Popescu said. “It is very, very sensitive to minute displacements in the membrane, down to the nanoscale.”
RBC membrane movement can be observed through typical light microscopes, a phenomenon known as “flickering,” but Popescu’s team was able not only to see nanoscale membrane fluctuations in live cells, but also to measure them quantitatively – a first.
In addition to normal cells, the team also measured two other morphologies: bumpy RBCs called echinocytes and round ones called spherocytes. They discovered that these deformed cells display less flexibility in their membranes, a finding that could provide insight into mechanics and treatment of diseases that affect RBC shape, such as malaria, sickle-cell disease and spherocytosis.
With collaborators from UCLA, the group used its data to construct a new model of the RBC membrane that accounts for fluctuations and curvature, a more complete and accurate rendering than previous models that treated the membrane as a flat sheet.
“Our measurements showed that a flat model could not explain the data. With this curvature model, we understand much better what is happening in the RBC,” said Popescu, adding, “It’s really a combination of a new optical method and new theoretical model, and that is what allowed us to find some new results where the shape and deformability are coupled.”
The team’s technique eventually could be used to screen for blood diseases such as malaria or to screen banked blood for membrane flexibility before transfusion, since stored blood often undergoes cellular shape changes.
In addition, this novel microscopy technique has important implications for researchers interested in membrane biology and dynamics, according to Catherine Best, co-author of the paper and instructor in the U. of I. College of Medicine. “An advantage to studying red blood cells in this way is that we can now look at the effects of chemical agents on membranes, specifically. It is very exciting. For instance, we can look at the membrane effects of alcohol, and we may learn something about tolerance to alcohol,” Best said.
Because diffraction phase microscopy measures live cells without physically manipulating or damaging them, it also could be used to evaluate medications being developed to treat blood cell morphology diseases, according to Popescu. “We can study the mechanics of a single cell under different pharmacological conditions, and I think that would be ideal for testing drugs,” he said.
The National Institutes of Health and the National Science Foundation funded this research, which included collaborators from MIT, Harvard Medical School, the University of Colorado, Harvard University and UCLA.
Liz Ahlberg | EurekAlert!
Can radar replace stethoscopes?
14.08.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Novel PET imaging method could track and guide therapy for type 1 diabetes
03.08.2018 | Society of Nuclear Medicine and Molecular Imaging
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
16.08.2018 | Information Technology
16.08.2018 | Health and Medicine
16.08.2018 | Information Technology