Surface area-to-volume ratio, not cellular rigidity, determines red blood cell traversal through small capillaries

Abstract

SummaryThe remarkable deformability of red blood cells (RBCs) depends on the viscoelasticity of the plasma membrane and cell contents and the surface area to volume (SA:V) ratio; however, it remains unclear which of these factors is the key determinant for passage through small capillaries. We used a microfluidic device to examine the traversal of normal, stiffened, swollen, parasitised and immature RBCs. We show that dramatic stiffening of RBCs had no measurable effect on their ability to traverse small channels. By contrast, a moderate decrease in the SA:V ratio had a marked effect on the equivalent cylinder diameter that is traversable by RBCs of similar stiffness. We developed a finite element model that provides a coherent rationale for the experimental observations, based on the nonlinear mechanical behaviour of the RBC membrane skeleton. We conclude that the SA:V ratio should be given more prominence in studies of RBC pathologies.

Robust fabrication of ultra-soft tunable PDMS microcapsules as a biomimetic model for red blood cells

“…Besides, to the best of our knowledge, only spherical objects have thus far been used in experiments to model RBCs, which adopt biconcave discoid shapes 22 at rest characterised by a reduced volume of 64% of that of a sphere with the same surface area. The reduced volume of RBCs has been shown both experimentally and numerically to considerably affect their ability to pass through confined microchannels 23 and deformation in shear flow. 24 The deformation and buckling of a spherical capsule as a function of reduced volume has been modelled 25 and validated with experiments on beach balls.…”