Erythrocytes' surface properties and stiffness predict survival and functional decline in ALS patients

Abstract

Erythrocytes play a fundamental role in oxygen delivery to tissues and binding to inflammatory mediators. Evidences suggest that dysregulated erythrocyte function could contribute to the pathophysiology of several neurodegenerative diseases. We aimed to evaluate changes in morphological, biomechanical, and biophysical properties of erythrocytes from amyotrophic lateral sclerosis (ALS) patients, as new areas of study in this disease. Blood samples were collected from ALS patients, comparing with healthy volunteers. Erythrocytes were assessed using atomic force microscopy (AFM) and zeta potential analysis. The patients' motor and respiratory functions were evaluated using the revised ALS Functional Rating Scale (ALSFRS‐R) and percentage of forced vital capacity (%FVC). Patient survival was also assessed. Erythrocyte surface roughness was significantly smoother in ALS patients, and this parameter was a predictor of faster decline in ALSFRS‐R scores. ALS patients exhibited higher erythrocyte stiffness, as indicated by reduced AFM tip penetration depth, which predicted a faster ALSFRS‐R score and respiratory subscore decay. A lower negative charge on the erythrocyte membrane was predictor of a faster ALSFRS‐R and FVC decline. Additionally, a larger erythrocyte surface area was an independent predictor of lower survival. These changes in morphological and biophysical membrane properties of ALS patients' erythrocytes, lead to increased cell stiffness and morphological variations. We speculate that these changes might precipitate motoneurons dysfunction and accelerate disease progression. Further studies should explore the molecular alterations related to these observations. Our findings may contribute to dissect the complex interplay between respiratory function, tissue hypoxia, progression rate, and survival in ALS.

Mechanism of hypoxia-induced damage to the mechanical property in human erythrocytes—band 3 phosphorylation and sulfhydryl oxidation of membrane proteins

“…Moreover, the deformability of erythrocytes has been increasingly studied for blood storage and transfusion in vitro (Koch et al, 2019;Yoshida et al, 2019;Barshtein et al, 2020;2021;Karafin et al, 2023), in addition to focusing on blood type, transfusion volume and blood quality. Based on the good deformability of red blood cells, the detection methods mainly include AFM to detect cell elasticity and EI index (Huisjes et al, 2018;Carelli-Alinovi et al, 2019;Yang et al, 2019;Lopes et al, 2023;Spinelli et al, 2023).…”