Novel assay finds new mechanism underlying red blood cell aging

Date:
September 21, 2021
Source:
Florida Atlantic University
Summary:
A multifaceted microfluidic in vitro assay is helping to identify
the role of hypoxia on red blood cell aging via the biomechanical
pathways.

It holds promise for investigating hypoxic effects on the metastatic
potential and relevant drug resistance of cancer cells. It also
can be a useful tool to predict the mechanical performance of
natural and artificial red blood cells for transfusion purposes
and to further extend to red blood cells in other blood diseases
and other cell types.



FULL STORY ==========================================================================
Red blood cells are the most abundant cell type in blood, carrying
oxygen throughout the human body. In blood circulation, they repetitively encounter various levels of oxygen tension. Hypoxia, a low oxygen tension condition, is a very common micro-environmental factor in physiological processes of blood circulation and various pathological processes such
as cancer, chronic inflammation, heart attacks and stroke. In addition,
an interplay between poor cellular deformability and impaired oxygen
delivery is found in various pathological processes such as sickle cell disease. Sickle red blood cells simultaneously undergo drastic mechanical deformation during the sickling and unsickling process.


==========================================================================
The interactions between hypoxia and cell biomechanics and the underlying biochemical mechanisms of the accelerated damage in diseased red blood
cells are well understood, however, the exact biomechanical consequences
of hypoxia contributing to red blood cell degradation (aging) remains
elusive.

Researchers from Florida Atlantic University's College of Engineering
and Computer Science, in collaboration with the Massachusetts Institute
of Technology (MIT), sought to identify the role of hypoxia on red blood
cell aging via the biomechanical pathways. In particular, they examined hypoxia- induced impairment of red blood cell deformability at the
single cell level, compared the differences between non-cyclic hypoxia
and cyclic hypoxia, and documented any cumulative effect vs. hypoxia
cycles, such as aspects that have not been studied quantitatively. Red
blood cell deformability is an important biomarker of its functionality.

For the study, published in the journal Lab on a Chip, researchers
developed a multifaceted microfluidic in vitroassay to precisely control
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 holds promise for investigating hypoxic effects on the metastatic potential
and relevant drug resistance of cancer cells. Cancer cells are more
metastatic in a hypoxic tumor microenvironment and cancer cell stiffness
has been shown to be an effective biomarker of their metastatic potential.

Findings from the study indicate an important biophysical mechanism
underlying red blood cell aging in which the cyclic hypoxia challenge
alone can lead to mechanical degradation of the red blood cell
membrane. This process in combination with the deformation-induced
mechanical fatigue represents two major fatigue loading conditions that circulating red blood cells experience.

"A unique feature of our system lies in that the cell deformability
measurement can be made on multiple, individually tracked red blood cells
under a well- controlled oxygen tension environment," said Sarah Du,
Ph.D., senior author, an associate professor in FAU's Department of Ocean
and Mechanical Engineering, and a member of FAU's Institute for Human
Health and Disease Intervention (I- HEALTH). "Our results showed that the deformability of red blood cells decreases under deoxygenation conditions
by before-and-after mechanical characterization of individual cells in
response to the switching of oxygen levels within a microfluidic device." Microfluidics serves as a miniaturized and efficient platform for gas
diffusion by interfacing the gas and aqueous solution through flow or
a gas-permeable membrane, which also is amenable to the control of the
cellular gaseous microenvironment.

For the study, researchers subjected red blood cells to a well-controlled repeated hypoxia microenvironment while allowing simultaneous
characterization of the cell mechanical properties. They integrated an electro-deformation technique into a microdiffusion chamber, which was
easy to implement and flexible in simultaneous applications of cyclic
hypoxia challenge and shear stresses on individual cells in suspension
and under quasi-stationary conditions.

Measurements of biomarkers, such as oxidative damage, can provide
additional information to establish quantitative relationships between
the fatigue loading and the biological processes, allowing a better understanding of red blood cell failure and aging. The microfluidic assay
also can 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 also can be a
useful tool to predict the mechanical performance of natural and
artificial red blood cells for transfusion purposes as well as to
assess the efficacy of relevant reagents in extending the cellular
lifespan in circulation," said Stella Batalama, Ph.D., dean, College
of Engineering and Computer Science. "This promising and cutting-edge
assay has the potential to further extend to red blood cells in other
blood diseases and other cell types." Study co-authors are Ming Dao,
Ph.D., Department of Materials Science and Engineering, MIT; Yuhao Qiang, Ph.D., FAU College of Engineering and Computer Science and currently
a postdoctoral researcher at MIT; and Jia Liu, Ph.D., FAU College of Engineering and Computer Science.

This research is based on the materials supported by the National
Science Foundation.

========================================================================== Story Source: Materials provided by Florida_Atlantic_University. Original written by Gisele Galoustian. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Yuhao Qiang, Jia Liu, Ming Dao, E. Du. In vitro assay for
single-cell
characterization of impaired deformability in red blood cells
under recurrent episodes of hypoxia. Lab on a Chip, 2021; 21 (18):
3458 DOI: 10.1039/d1lc00598g ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210921091738.htm

--- up 2 weeks, 5 days, 8 hours, 25 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)