Quantifying the biophysical properties of stomatocytes in health and disease

2026-06-02

AI Summary

Hereditary stomatocytosis (HS) poses challenges in predicting splenectomy outcomes due to fragmented measurements of red blood cell (RBC) mechanical properties. This study integrates dissipative particle dynamics simulations with microfluidic imaging to develop unified models of healthy and three stomatocytic RBC variants, incorporating single-cell mechanics, splenic filtration, and whole-blood rheology within a single framework. The results demonstrate that RBC geometry predominantly governs transit through endothelial slits: overhydrated cells require an order-of-magnitude higher pressure than normal cells, while dehydrated cells traverse more easily but increase low-shear whole-blood viscosity by 29%. The developed microfluidic chip enables label-free separation of the four RBC types with a resolution of up to 4.5 standard deviations, offering a novel strategy for preoperative risk stratification.

Abstract

Hereditary stomatocytosis (HS) comprises red blood cell (RBC) disorders characterized by cup-shaped erythrocytes that respond oppositely to splenectomy: curative in overhydrated HS (OHS) but potentially thrombogenic in dehydrated HS (DHS/xerocytosis). This paradox persists because RBC biomechanics is governed by partly independent parameters--shear modulus, bending rigidity, surface-to-volume ratio (S/V), and cytoplasmic viscosity--that existing assays capture only piecemeal. Here we combine dissipative particle dynamics (DPD) simulations with microfluidic imaging to construct a control discocyte and three stomatocyte models (ST-RBC1-3) at fixed membrane area and decreasing volume (109.7, 101.5, 89.8 fL), spanning the OHS-to-DHS range. Tracing this parameter set through five mechanically orthogonal assays, we find that interendothelial-slit (IES) traversal is geometry-dominated: overhydrated ST-RBC1 requires an order of magnitude higher critical pressure than healthy RBCs, whereas dehydrated ST-RBC3 passes freely. ST-RBC3 nonetheless suppresses membrane tank-treading and raises low-shear whole-blood viscosity by ~29% at physiological haematocrit, comparable to Gaucher-disease hyperviscosity. A funnel-obstacle chip amplifies these differences into a label-free centerline-offset signal predicted to separate all four RBC types (~4.5 standard deviations between extreme phenotypes). These results unite single-cell mechanics, splenic filtration, and hemorheology in one framework, resolve the splenectomy paradox, and point toward microfluidic pre-operative risk stratification in HS.

Problem

• hereditary stomatocytosis
• red blood cell biomechanics
• splenectomy paradox
• hemorheology
• microfluidics

Innovation

• microfluidics
• dissipative particle dynamics
• stomatocytosis
• hemorheology
• splenic filtration