Estimation of membrane bending modulus of stiffness tuned human red blood cells from micropore filtration studies.

Rekha Selvan,Sarbari Bhattacharya,Shruthi S Iyengar,Praveen Parthasarathi,Sharath Ananthamurthy,Fang-Bao Tian

doi:10.1371/journal.pone.0226640

Rekha Selvan, Sarbari Bhattacharya + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0226640

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Abstract

Human red blood cells (RBCs) need to deform in order to pass through capillaries in human vasculature with diameter smaller than that of the RBC. An altered RBC cell membrane stiffness (CMS), thereby, is likely to have consequences on their flow rate. RBC CMS is known to be affected by several commonly encountered disease conditions. This study was carried out to investigate whether an increase in RBC CMS, to the extent seen in such commonly encountered medical conditions, affects the RBC flow rate through channels with diameters comparable to that of the RBC. To do this, we use RBCs extracted from a healthy individual with no known medical conditions and treated with various concentrations of Bovine Serum Albumin (BSA). We study their flow through polycarbonate membranes with pores of diameter 5μm and 8μm which are smaller than and comparable to the RBC diameter respectively. The studies are carried out at constant hematocrit and volumetric flow rate. We find that when the diameter of the capillary is smaller than that of the RBC, the flow rate of the RBCs is lowered as the concentration of BSA is increased while the reverse is true when the diameter is comparable to that of the RBC. We confirm that this is a consequence of altered CMS of the RBCs from their reorientation dynamics in an Optical Tweezer. We find that a treatment with 0.50mg/ml BSA mimics the situation for RBCs extracted from a healthy individual while concentrations higher than 0.50mg/ml elevate the RBC CMS across a range expected for individuals with a condition of hyperglycemia. Using a simple theoretical model of the RBC deformation process at the entry of a narrow channel, we extract the RBC membrane bending modulus from their flow rate.

Highlights

Human blood consists of plasma, red blood cells (RBCs), white blood cells (WBCs) and platelets
We find that the flow rate of RBCs is clearly affected by Bovine Serum Albumin (BSA) treatment, the exact manner of change depending on whether the RBC diameter is larger or smaller than the channel diameter
The elevated cell membrane stiffness (CMS) can mimic the RBC CMS observed for individuals with a medical condition of hyperglycemia

Summary

Introduction

Human blood consists of plasma, red blood cells (RBCs), white blood cells (WBCs) and platelets. These have been widely reported in literature and involve a wide variety of techniques based on micro pipette aspiration [11,12,13], optical tweezers (reorientation [14], stretching [15,16,17]), observation of membrane fluctuations [18, 19], optical stretcher [20, 21] and micro fluidic channel flows [3, 22, 23] Though all these techniques, in principle, provide a measure of the RBC CMS, the stress regimes in which the experiments are done are extremely different and can lead to a varied conclusion on the viscoelastic response of the RBC. We obtain an estimate of membrane bending modulus of bRBCs using a simple theoretical model that assumes an axisymmetric shape on deformation and imposes a constraint of constant surface area throughout the deformation process

Materials and methods

Conclusions