Quantifying the biophysical properties of stomatocytes in health and disease
For clinicians managing hereditary stomatocytosis, this work provides a unified biomechanical framework to predict splenectomy outcomes and suggests a microfluidic risk stratification tool.
The study combines DPD simulations and microfluidic imaging to quantify biomechanical differences between healthy and stomatocytic red blood cells, finding that overhydrated stomatocytes require an order of magnitude higher critical pressure for splenic passage while dehydrated ones pass freely but increase whole-blood viscosity by ~29%, resolving the splenectomy paradox and enabling label-free separation of phenotypes.
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.