Mapping viscoelastic properties of healthy and pathological red blood cells at the nanoscale level

Abstract

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.

Correlated Disorder in Myelinated Axons Orientational Geometry and Structure

“…This makes standard experimental probes probing the average structure inadequate for the visualization of this heterogeneity, requiring highly spatially resolved probes. Biological tissues are typically intrinsically heterogeneous; indeed, nowadays new features and properties have been visualized using scanning methods with high spatial resolutions, such as by Atomic Force Microscopy [38][39][40], Confocal Microscopy [40], Scanning Electron Microscopy [35] and Scanning micro X-ray diffraction [15][16][17][18][19][20][21]. Correlated spatial structural fluctuations in biological systems have been correlated with the emergence of quantum coherence in biological matter [35,41], in photosystems [42] and intrinsically disordered proteins [43,44], as well as in lamellar oxides showing quantum coherence [45][46][47][48], where non-Euclidean spatial geometries for signal transmission are able to emerge from a correlated disorder [22,48].…”

Biolens behavior of RBCs under optically‐induced mechanical stress

“…Similarly, the morphology of cells is of key importance for aging issues, deformability/elasticity analysis and diagnostic purposes. Thus, alterations of both mechanical and morphological properties in RBCs have been regarded as direct indicators of blood quality (4,5) and, for these reasons, are subject of intense and worldwide studies (6)(7)(8). The development of non-invasive methods that enable the identification of morphological and biomechanical variations of RBCs is thus of utmost scientific and medical interest.…”

“…Several methods have been developed for investigating the difference of the mechanical properties of healthy and sick RBCs. Common techniques for addressing this purpose are based on particular microfluidic channels (10)(11)(12)(13), and on various electrical/optical techniques, such as atomic force microscopy (4,14), dielectrophoresis (15), and optical trapping techniques (16)(17)(18)(19)(20)(21). For example, parachute and slipper shapes are produced, respectively, in small and large one-dimensional microchannels (22), while opticallyinduced deformation using the optical stretcher is typically limited to cell elongation along a defined direction due to the applied antipodal stretching forces (19,23).…”

Modeling of biomechanics and biorheology of red blood cells in type-2 diabetes mellitus

“…In addition, several studies using atomic force microscopy (AFM) directly examined the biomechanical properties of diabetic RBCs and demonstrated that they are less deformable than normal RBCs (Fig. 1), which could be due to the oxidation and glycosylation of hemoglobin and proteins on cell membrane under abnormal glycemic condition (16)(17)(18).…”