An RBC-MsUQ Framework for Red Blood Cell Morpho-Mechanics

Abstract

Characterizing the morpho-mechanical properties of red blood cells (RBCs) is crucial for understanding microvascular transport mechanisms and cellular pathophysiological processes, yet current computational models are constrained by multi-source uncertainties including cross-platform experimental discrepancies and parameter identification stochasticity. We present RBC-MsUQ, a novel multi-stage uncertainty quantification framework tailored for RBCs. It integrates hierarchical Bayesian inference with diverse experimental datasets, establishing prior distributions for RBC parameters via microscopic simulations and literature-derived data. A dynamic annealing technique defines stress-free baselines, while deep neural network surrogates, optimized through sensitivity analysis, achieve sub-10$^{-2}$ prediction errors for efficient simulation approximation. Its two-stage hierarchical inference architecture constrains geometric and shear modulus parameters using stress-free state and stretching data in Stage I and enables full-parameter identification via membrane fluctuation and relaxation tests in Stage II. Applied to healthy and malaria-infected RBCs, the RBC-MsUQ framework produces statistically robust posterior distributions, revealing increased stiffness and viscosity in pathological cells. Quantitative model-experiment validation demonstrates that RBC-MsUQ effectively mitigates uncertainties through cross-platform data fusion, overcoming the critical limitations of existing computational approaches. The RBC-MsUQ framework thus provides a systematic paradigm for studying RBC properties and advancing cellular mechanics and biomedical engineering.