Active modulation of human erythrocyte mechanics
- 1 August 2020
- journal article
- review article
- Published by American Physiological Society in American Journal of Physiology-Cell Physiology
- Vol. 319 (2), C250-C257
- https://doi.org/10.1152/ajpcell.00210.2020
Abstract
The classic view of the red blood cell (RBC) presents a biologically inert cell that upon maturation has limited capacity to alter its physical properties. This view developed largely because of the absence of translational machinery and inability to synthesize or repair proteins in circulating RBC. Recent developments have challenged this perspective, in light of observations supporting the importance of posttranslational modifications and greater understanding of ion movement in these cells, that each regulate a myriad of cellular properties. There is thus now sufficient evidence to induce a step change in understanding of RBC: rather than passively responding to the surrounding environment, these cells have the capacity to actively regulate their physical properties and thus alter flow behavior of blood. Specific evidence supports that the physical and rheological properties of RBC are subject to active modulation, primarily by the second-messenger molecules nitric oxide (NO) and calcium-ions (Ca2+). Furthermore, an isoform of nitric oxide synthase is expressed in RBC (RBC-NOS), which has been recently demonstrated to have an active role in regulating the physical properties of RBC. Mechanical stimulation of the cell membrane activates RBC-NOS, leading to NO generation, which has several intracellular effects, including the S-nitrosylation of integral membrane components. Intracellular concentration of Ca2+ is increased upon mechanical stimulation via the recently identified mechanosensitive cation channel piezo1. Increased intracellular Ca2+ modifies the physical properties of RBC by regulating cell volume and potentially altering several important intracellular proteins. A synthesis of recent advances in understanding of molecular processes within RBC thus challenges the classic view of these cells and rather indicates a highly active cell with self-regulated mechanical properties.Keywords
This publication has 59 references indexed in Scilit:
- Calcium in Red Blood Cells—A Perilous BalanceInternational Journal of Molecular Sciences, 2013
- RBC-NOS-Dependent S-Nitrosylation of Cytoskeletal Proteins Improves RBC DeformabilityPLOS ONE, 2013
- Moderate Exercise Promotes Human RBC-NOS Activity, NO Production and Deformability through Akt Kinase PathwayPLOS ONE, 2012
- A Quantitative Comparison of Mechanical Blood Damage Parameters in Rotary Ventricular Assist Devices: Shear Stress, Exposure Time and Hemolysis IndexJournal of Biomechanical Engineering, 2012
- The Mechanosensitive Ion Channel Piezo1 Is Inhibited by the Peptide GsMTx4Biochemistry, 2011
- Shear stress activation of nitric oxide synthase and increased nitric oxide levels in human red blood cellsNitric Oxide, 2011
- Local Membrane Deformations Activate Ca2+-Dependent K+ and Anionic Currents in Intact Human Red Blood CellsPLOS ONE, 2010
- Cytoskeletal coherence requires myosin-IIA contractilityJournal of Cell Science, 2010
- Functional significance of differential eNOS translocationAmerican Journal of Physiology-Heart and Circulatory Physiology, 2006
- Effect of red blood cell shape on oxygen transport in capillariesMathematical Biosciences, 1993