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

Abstract

Erythrocytes in patients with type-2 diabetes mellitus (T2DM) are associated with reduced cell deformability and elevated blood viscosity, which contribute to impaired blood flow and other pathophysiological aspects of diabetesrelated vascular complications. In this study, by using a two-component red blood cell (RBC) model and systematic parameter variation, we perform detailed computational simulations to probe the alteration of the biomechanical, rheological and dynamic behavior of T2DM RBCs in response to morphological change and membrane stiffening. First, we examine the elastic response of T2DM RBCs subject to static tensile forcing and their viscoelastic relaxation response upon release of the stretching force. Second, we investigate the membrane fluctuations of T2DM RBCs and explore the effect of cell shape on the fluctuation amplitudes. Third, we subject the T2DM RBCs to shear flow and probe the effects of cell shape and effective membrane viscosity on their tank-treading movement. In addition, we model the cell dynamic behavior in a microfluidic channel with constriction and quantify the biorheological properties of individual T2DM RBCs. Finally, we simulate T2DM RBC suspensions under shear and compare the predicted viscosity with experimental measurements. Taken together these simulation results and their comparison with currently available experimental data are helpful in identifying a specific parametric model -the first of its kind -that best describes the main hallmarks of T2DM RBCs, which can be used in future simulation studies of hematologic complications of T2DM patients.

Optic nerve head perfusion changes preceding peripapillary retinal nerve fibre layer thinning in preclinical diabetic retinopathy

“…For example, retinal vascular endothelial cells may have impaired ability to liberate endothelial nitric oxide synthase, thus affecting retinal vascular autoregulation. In addition, enhanced plasma viscosity, increased platelet aggregation, and decreased red blood cell deformability also lead to retinal and ONH perfusion problems . Fundamental structural alterations of capillaries in diabetes including endothelium dysfunction, vascular basement membrane thickening, pericyte apoptosis and capillary occlusion also involve small blood vessels in the ONH …”

Quantifying Platelet Margination in Diabetic Blood Flow

“…We found that, in agreement with the experiments, margination of micro-beads increases with size and shear rate. We have introduced and validated a T2DM RBC model in our previous work (47). Here, we adopted the same red cell model for modeling the diabetic blood, whereas a T2DM platelet model is built based on the parameters informed by the clinical blood analysis of 64 diabetic patients.…”

“…Although the alteration in the size and shape of diabetic RBCs is still debatable and probably dependent on glycemic control of the study subjects, we considered extreme values for S/V that reported by Jin et al (56). We have recently proposed a T2DM RBC model (47), which has been validated with available experimental data. Following our previous study, here, we extend our T2DM RBC model (DRBC) to a suspension with cell properties similar to those of a NRBC except for a shear modulus, µ s = 2µ 0 (µ 0 is the shear modulus of healthy subjects), and a reduced S/V ratio, S/V = 1.04.…”