Investigation of red blood cell mechanical properties using AFM indentation and coarse-grained particle method

Abstract

BackgroundRed blood cells (RBCs) deform significantly and repeatedly when passing through narrow capillaries and delivering dioxygen throughout the body. Deformability of RBCs is a key characteristic, largely governed by the mechanical properties of the cell membrane. This study investigated RBC mechanical properties using atomic force microscopy (AFM) with the aim to develop a coarse-grained particle method model to study for the first time RBC indentation in both 2D and 3D. This new model has the potential to be applied to further investigate the local deformability of RBCs, with accurate control over adhesion, probe geometry and position of applied force.ResultsThe model considers the linear stretch capacity of the cytoskeleton, bending resistance and areal incompressibility of the bilayer, and volumetric incompressibility of the internal fluid. The model’s performance was validated against force–deformation experiments performed on RBCs under spherical AFM indentation. The model was then used to investigate the mechanisms which absorbed energy through the indentation stroke, and the impact of varying stiffness coefficients on the measured deformability. This study found the membrane’s bending stiffness was most influential in controlling RBC physical behaviour for indentations of up to 200 nm.ConclusionsAs the bilayer provides bending resistance, this infers that structural changes within the bilayer are responsible for the deformability changes experienced by deteriorating RBCs. The numerical model presented here established a foundation for future investigations into changes within the membrane that cause differences in stiffness between healthy and deteriorating RBCs, which have already been measured experimentally with AFM.Electronic supplementary materialThe online version of this article (10.1186/s12938-017-0429-5) contains supplementary material, which is available to authorized users.

Searching for the Mechanical Fingerprint of Pre-diabetes in T1DM: A Case Report Study

“…In a previous study, we used AFM to investigate the effects of type 2 diabetes mellitus (T2DM) on RBC mechanical properties, demonstrating an increase in cell stiffness and hysteresis for the T2DM cohort compared to the healthy subjects (Ciasca et al, 2015). Such a stiffening was consistent with the results previously discussed in the papers of Pretorius and co-workers (Buys et al, 2013;Pretorius and Kell, 2014;Pretorius et al, 2015;Visser et al, 2017) and with similar AFM studies summarized in Table 1 (Gillies and Prestidge, 2004;Lekka et al, 2005;Dulińska et al, 2006;Fornal et al, 2006;Girasole et al, 2012;Li et al, 2012;Lamzin and Khayrullin, 2014;Ciasca et al, 2015;Pretorius et al, 2015;Zhang et al, 2015;Barns et al, 2017). In the recent paper from Loyola-Leyva et al (2018), mechanical measurements carried out on RBCs obtained from diabetic and control subjects with techniques other than AFM are also reviewed.…”

Optical Tweezer Stretching of Miniature Coarse-Grained Red Blood Cells

“…To date, most CG particle models of RBCs have only been validated qualitatively, by studying their shape at rest and under flow conditions (19). To determine the membrane shear modulus, experimental techniques typically involve applying some external force in order to deform it.…”

Nonlinear Biomechanical Characteristics of Deep Deformation of Native RBC Membranes in Normal State and under Modifier Action

“…The mechanical properties and structural organization of membranes determine the functional state of red blood cells (RBCs). Deformability is one of the key physiological and biophysical indicators of RBC [1]. Changes of the mechanical characteristics of cell membranes can lead to a decrease in the rate of capillary blood flow and to development of stagnant phenomena in the microcirculation, and it can also reduce the amount of oxygen delivered to the tissues.…”