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In physiological conditions, red blood cells (RBCs) demonstrate remarkable deformability, allowing them to undergo considerable deformation when passing through the microcirculation. However, this deformability is compromised in Type 1 diabetes mellitus (T1DM) and related pathological conditions. This study aims to investigate the biomechanical properties of RBCs in T1DM patients, focusing on identifying significant mechanical alterations associated with microvascular complications (MCs). We conducted a case-control study involving 38 T1DM subjects recruited from the Diabetes Care Unit at Fondazione Policlinico Gemelli Hospital, comprising 22 without MCs (control group) and 16 with MCs (pathological group). Atomic Force Microscopy was employed to assess RBC biomechanical properties in a liquid environment. We observed significant RBC stiffening in individuals with MCs, particularly during large indentations that mimic microcirculatory deformations. Univariate analysis unveiled significant differences in RBC stiffness (median difference 0.0006 N/m, p = 0.012) and RBC counts (median difference -0.39 × 10 12 /L, p = 0.009) between the MC and control groups. Bivariate logistic regression further demonstrated that combining these parameters could effectively discriminate between MC and non-MC conditions, achieving an AUC of 0.82 (95% CI: 0.67-0.97). These findings reveal the potential of RBC biomechanical properties as diagnostic and monitoring tools in diabetes research. Exploring RBC mechanical alterations may lead to the development of novel biomarkers, which, in combination with clinical markers, could facilitate the early diagnosis of diabetes-related complications.

Fast diagnostic methods are crucial to reduce the burden on healthcare systems. Currently, detection of diabetes complications such as neuropathy requires time-consuming approaches to observe the correlated red blood cells (RBCs) morphological changes. To tackle this issue, an optical analysis of RBCs in air was conducted in the 250-2500 nm range. The distinct oscillations present in the scattered and direct transmittance spectra have been analyzed with both Mie theory and anomalous diffraction approximation. The results provide information about the swelling at the ends of RBCs and directly relate the optical data to RBCs morphology and deformability. Both models agree on a reduction in the size and deformability of RBCs in diabetic patients, thus opening the way to diabetes diagnosis and disease progression assessment., (© 2024 The Author(s). Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

In physiological conditions, red blood cells (RBCs) are capable of dramatic deformations when passing through the microvasculature. This extreme deformability is closely related to the RBC biconcave shape, to the fluidic nature of the haemoglobin and the cell membrane structure, primarily consisting of a phospholipid bilayer with an underlying two-dimensional spectrin network. In many pathological and inflammatory conditions, the shape and the extreme deformability of erythrocytes appear to be significantly altered. These findings have stimulated intense research towards the search and validation of novel erythrocyte-based mechanical biomarkers, useful for disease diagnosis and therapy monitoring. In this study, we investigated with Atomic Force Microscopy (AFM) the mechanical properties of erythrocytes obtained from a 68 years old cirrhotic man diagnosed with spur cell anaemia and cold agglutinated disease, before and after liver transplantation. Mechanical changes are compared with ultrastructural alterations as studied by scanning electron microscopy and discussed according to confocal fluorescence microscopy results, showing possible alterations induced by the cirrhotic environment at the level of the RBCs cytoskeletal organisation and lipidic composition. Taken together, the results here presented show that liver transplantation not only contributes to restoring the proper RBC morphology, but it also induces recovery of the physiological viscous behaviour of cells, further stressing the relevance of viscous and dissipative forces in determining the RBC biomechanical response., (© 2020 Royal Microscopical Society.)

In order to pass through the microcirculation, red blood cells (RBCs) need to undergo extensive deformations and to recover the original shape. This extreme deformability is altered by various pathological conditions. On the other hand, an altered RBC deformability can have major effects on blood flow and can lead to pathological implications. The study of the viscoelastic response of red blood cells to mechanical stimuli is crucial to fully understand deformability changes under pathological conditions. However, the typical erythrocyte biconcave shape hints to a complex and intrinsically heterogeneous mechanical response that must be investigated by using probes at the nanoscale level. In this work, the local viscoelastic behaviour of healthy and pathological red blood cells was probed by Atomic Force Microscopy (AFM). Our results clearly show that the RBC stiffness is not spatially homogeneous, suggesting a strong correlation with the erythrocyte biconcave shape. Moreover, our nanoscale mapping highlights the key role played by viscous forces, demonstrating that RBCs do not behave as pure elastic bodies. The fundamental role played by viscous forces is further strengthened by the comparison between healthy and pathological (diabetes mellitus) RBCs. It is well known that pathological RBCs are usually stiffer than the healthy ones. Our measures unveil a more complex scenario according to which the difference between normal and pathological red blood cells does not merely lie in their stiffness but also in a different dynamical response to external stimuli that is governed by viscous forces.