Researchers seek to identify role of hypoxia in aging red blood cells
Red blood cells are the most abundant type of cell in the blood, carrying oxygen throughout the human body. In the bloodstream, they repeatedly encounter varying levels of oxygen tension. Hypoxia, a condition of low oxygen tension, is a very common micro-environmental factor in the physiological processes of the bloodstream and various pathological processes such as cancer, chronic inflammation, heart attacks and strokes. .
In addition, an interaction between poor cell deformability and impaired oxygen supply is found in various pathological processes such as sickle cell anemia. Sickle red blood cells simultaneously undergo drastic mechanical deformation during the sickle and sickle cell processes.
The interactions between hypoxia and cellular biomechanics and the biochemical mechanisms underlying accelerated damage in diseased red blood cells are well understood, however, the exact biomechanical consequences of hypoxia contributing to red blood cell degradation (aging) remain. elusive.
Researchers from the College of Engineering and Computer Science at Florida Atlantic University, in collaboration with the Massachusetts Institute of Technology (MIT), sought to identify the role of hypoxia on the aging of red blood cells via biomechanical pathways.
In particular, they examined the hypoxia-induced alteration of red blood cell deformability at the individual cell level, compared the differences between non-cyclic hypoxia and cyclic hypoxia, and documented any cumulative effect compared to. cycles of hypoxia, such as aspects that have not been studied quantitatively. The deformability of red blood cells is an important biomarker of their functionality.
For the study, published in the journal Lab-on-a-chip, researchers have developed a multifaceted microfluidic system in vitro test to accurately monitor the gaseous environment while probing the mechanical performance of red blood cells, which can be used as a characterization tool for other cell types involved in oxygen-dependent biological processes.
The assay shows promise for studying hypoxic effects on the metastatic potential and resistance to relevant drugs of cancer cells. Cancer cells are more metastatic in a hypoxic tumor microenvironment, and the rigidity of cancer cells has been shown to be an effective biomarker of their metastatic potential.
The results of the study indicate an important biophysical mechanism underlying the aging of red blood cells in which the challenge of cyclic hypoxia alone can lead to mechanical degradation of the red blood cell membrane. This process, combined with strain-induced mechanical fatigue, represent two major fatigue loading conditions that circulating red blood cells experience.
“A unique feature of our system is that the measurement of cell deformability can be performed on multiple red blood cells tracked individually in a well-controlled oxygen stress environment,” said Sarah Du, Ph.D., author Principal, Associate Professor in the Department of Oceanic and Mechanical Engineering at FAU, and Member of the FAU Institute for Human Health and Disease Response (I-HEALTH).
Our results showed that red blood cell deformability decreases under deoxygenated conditions by mechanical characterization before and after individual cells in response to switching oxygen levels in a microfluidic device. “
Sarah Du, Ph.D., study lead author and associate professor, Department of Oceanic and Mechanical Engineering, Florida Atlantic University
Microfluidics serves as a miniaturized and efficient platform for gas diffusion by interfacing the gas and the aqueous solution through a gas-permeable flow or membrane, which also lends itself to the control of the cellular gaseous microenvironment.
For the study, the researchers subjected the red blood cells to a well-controlled repeated hypoxia microenvironment while allowing simultaneous characterization of the mechanical properties of the cells. They incorporated an electrodeformation technique into a microdiffusion chamber, easy to implement and flexible in simultaneous applications of cyclic hypoxia challenge and shear stress on single cells in suspension and under quasi-stationary conditions.
Measurements of biomarkers, such as oxidative damage, can provide additional information to establish quantitative relationships between fatigue load and biological processes, allowing a better understanding of red blood cell failure and aging. The microfluidic assay can also be extended to study other types of biological cells for their mechanical performance and response to gaseous environments.
“The unique method developed by Professor Du’s lab may also be a useful tool for predicting the mechanical performance of natural and artificial red blood cells for transfusion as well as for evaluating the effectiveness of relevant reagents in prolonging cell life. outstanding, ”said Stella Batalama, Ph.D., Dean, College of Engineering and Computer Science. “This promising and cutting-edge test has the potential to extend further to red blood cells in other diseases of the blood and other cell types.”
Atlantic University of Florida
Qiang, Y., et al. (2021) In vitro assay for the single-cell characterization of altered red blood cell deformability during recurrent episodes of hypoxia. Lab-on-a-chip. doi.org/10.1039/D1LC00598G.