Nanoscale Mapping of the Biomechanical Behavior in Healthy and Pathological Erythrocytes

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. Altered RBC deformability have major effects on blood flow and 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 RBCs was probed by Atomic Force Microscopy. Our results show that the RBC stiffness is not spatially homogeneous, suggesting a strong correlation with the erythrocyte biconcave shape. 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 RBCs does not merely lie in their stiffness but also in a different dynamical response to external stimuli that is governed by viscous forces. From a clinical point of view novel mechanobiological markers of diseases are currently based on the measurement of the average RBC stifness. Our results show that both the local stiffness distribution and the viscoelastic response not only provide important information on the RBC biomechanics but also can be more effective than the average Young's modulus in distinguishing between healthy and pathological RBCs.