The dynamic behavior of chemically “stiffened” red blood cells in microchannel flows
Abstract
The rigidity of red blood cells (RBCs) plays an important role in whole blood viscosity and is correlated with several cardiovascular diseases. Two chemical agents that are commonly used to study cell deformation are diamide and glutaraldehyde. Despite diamide's common usage, there are discrepancies in the literature surrounding diamide's effect on the deformation of RBCs in shear and pressure-driven flows; in particular, shear flow experiments have shown that diamide stiffens cells, while pressure-driven flow in capillaries did not give this result. We performed pressure-driven flow experiments with RBCs in a microfluidic constriction and quantified the cell dynamics using high-speed imaging. Diamide, which affects RBCs by cross-linking spectrin skeletal membrane proteins, did not reduce deformation and showed an unchanged effective strain rate when compared to healthy cells. In contrast, glutaraldehyde, which is a non-specific fixative that acts on all components of the cell, did reduce deformation and showed increased instances of tumbling, both of which are characteristic features of stiffened, or rigidified, cells. Because glutaraldehyde increases the effective viscosity of the cytoplasm and lipid membrane while diamide does not, one possible explanation for our results is that viscous effects in the cytoplasm and/or lipid membrane are a dominant factor in dictating dynamic responses of RBCs in pressure-driven flows. Finally, literature on the use of diamide as a stiffening agent is summarized, and provides supporting evidence for our conclusions.
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Loss of deformability in RBCs may increase blood viscosity significantly due to increased end-over-end tumbling.
“a loss of deformability in RBCs may increase viscosity significantly (34) due to increased end-over-end tumbling (61).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [61]
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Self-citation
- Authors
- Forsyth, A. M., Wan, J., Ristenpart, W. D., & Stone, H. A.
- Affiliations
- Harvard University (US)
- Princeton University (US)
- University of California, Davis (US)
- Corresponding author
- Stone, Howard A.
- Venue
- Microvascular Research
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 80
- Issue
- 1
- Pages
- 37-43
- ISSN
- 0026-2862 (ISSN-L)
- OpenAlex
- W2134443550
- Cited by
- 172
- References
- 43
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 7 · 2023: 11 · 2022: 10 · 2021: 9 · 2020: 14 · 2019: 16 · 2018: 11 · 2017: 14 · 2016: 11 · 2015: 15 · 2014: 14 · 2013: 9 · 2012: 10
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Microvascular Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Harvard University
- Materials Research Science and Engineering Center, Harvard University
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
- Physical Sciences › Chemical Engineering › Fluid Flow and Transfer Processes › Rheology and Fluid Dynamics Studies
- Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
- Keywords
- erythrocyte deformability, cell stiffness, diamide, glutaraldehyde, pressure-driven flow, cytoplasmic viscosity, membrane viscosity, shear flow, blood viscosity
- MeSH terms
- Cytoplasm, Diamide, Elasticity, Erythrocyte Deformability, Erythrocyte Membrane, Erythrocytes, Glutaral, Humans, Motion, Viscosity, Hemorheology, Microfluidics, Microfluidic Analytical Techniques
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