The impact of pathological factors on the structure and function of erythrocyte membranes: from the molecular level to clinical consequences

Background. Red blood cells play a key role in gas transport and tissue oxygenation. Pathological alterations in the structure and function of erythrocyte membranes lead to impaired deformability, reduced ability to traverse microvessels, and microcirculatory failure. Oxidative stress, lipid peroxidation, and changes in membrane lipid composition significantly affect oxygen delivery, contribute to chronic hypoxia, and exacerbate systemic diseases, including cardiovascular, neurodegenerative disorders, and complications of infectious diseases, notably COVID-19. Purpose – to characterize the effects of pathological factors on erythrocyte membrane deformability, stiffness, and lipid composition, and to determine their relationship with oxygen transport, microcirculation, and disease progression. Materials and Methods. A systematic review of scientific literature was conducted using PubMed, Clinical Key Elsevier, Cochrane Library, Google Scholar. Search terms included: erythrocyte deformability, lipid peroxidation, oxidative stress, red blood cell membrane biophysics, shear stress, microcirculation, hypoxia, metabolic syndrome. Studies were selected based on experimental data, modern research methods (electron microscopy, atomic force microscopy, fluorescence spectroscopy, biophysical modeling), and relevance to the topic. Results. Pathological factors such as oxidative stress, lipid metabolism disorders, mechanical stress, and infections lead to reduced erythrocyte deformability, increased membrane stiffness, alterations in lipid composition with an imbalance between saturated and unsaturated fatty acids, and accumulation of lipid peroxidation products. Impaired deformability compromises microcirculation, increases blood viscosity, promotes hypoxia, and exacerbates tissue ischemia. The most pronounced changes are observed in patients with cardiovascular diseases, diabetes, neurodegeneration, obesity, and infectious diseases (SARS-CoV-2). Modeling erythrocyte behavior in narrow capillaries highlights the critical importance of surface area-to-volume ratio for cell deformability. Reduced flexibility is associated with dysregulated mechanosensitive ion channels, eryptosis activation, microparticle release, and homeostasis disruption. Physical exertion, aging, and cryopreservation also significantly affect membrane properties, underscoring their relevance to clinical practice and transfusion medicine. Conclusions. Pathological changes in erythrocyte membranes are critical in microcirculatory dysfunction, chronic hypoxia, and systemic disease progression. Understanding the mechanobiology of erythrocytes offers opportunities for early diagnosis, monitoring, and therapy development aimed at preserving red cell function, preventing complications, and improving patient outcomes.