Persistent red blood cells retain their ability to move in microcapillaries under high levels of oxidative stress

Abstract

Oxidative stress is one of the key factors that leads to red blood cells (RBCs) aging, and impairs their biomechanics and oxygen delivery. It occurs during numerous pathological processes and causes anaemia, one of the most frequent side effects of cancer chemotherapy. Here, we used microfluidics to simulate the microcirculation of RBCs under oxidative stress induced by tert-Butyl hydroperoxide. Oxidative stress was expected to make RBCs more rigid, which would lead to decrease their transit velocity in microfluidic channels. However, single-cell tracking combined with cytological and AFM studies reveals cell heterogeneity, which increases with the level of oxidative stress. The data indicates that the built-in antioxidant defence system has a limit exceeding which haemoglobin oxidation, membrane, and cytoskeleton transformation occurs. It leads to cell swelling, increased stiffness and adhesion, resulting in a decrease in the transit velocity in microcapillaries. However, even at high levels of oxidative stress, there are persistent cells in the population with an undisturbed biophysical phenotype that retain the ability to move in microcapillaries. Developed microfluidic analysis can be used to determine RBCs’ antioxidant capacity for the minimization of anaemia during cancer chemotherapy.

Erythrocyte metabolism

“…552 Based on the above calculations, faster lung-to-lung cycles cannot fully account for the younger erythrocytes in athletes and other factors affecting lifespan may also be at play. 487,551,[553][554][555][556][557][558] It is characteristic that erythrocytes can get mechanically compromised by foot impact in runners, particularly in the capillaries on the soles of their feet, and this mechanical trauma represents a primary cause of haemolysis during running. 559 Example 3.…”

Advances in Microfluidics for Single Red Blood Cell Analysis

“…On the other hand, Atomic Force Microscopy (AFM) has been reported to efficiently assess RBC stiffness and ability to move in microcapillaries after being exposed to intravenous fluid (IVF) [43,44] or high levels of oxidative stress [45]. [27].…”

“…These tomography tools enable the label-free specific 3D tomography of biological samples through hyperspectral optical diffraction techniques [51]. On the other hand, Atomic Force Microscopy (AFM) has been reported to efficiently assess RBC stiffness and ability to move in microcapillaries after being exposed to intravenous fluid (IVF) [43,44] or high levels of oxidative stress [45].…”

RBC-GEM: a Knowledge Base for Systems Biology of Human Red Blood Cell Metabolism

“…Each transit cycle takes approximately one minute. RBCs thus are subjected to constantly changing environmental stresses that exacerbate damage and degradation of proteins, from elevated oxidant stress in the lung, to hypoxia and shear stress when traversing capillaries as narrow as 5 μm[2]. The RBC lacks the machinery necessary to synthesize new proteins de novo ; consequently, the RBC proteome loses functionality over time, affecting essential functions in gas transport.…”