Quantifying reticulocyte biomechanics in health and disease

Red blood cell (RBC) populations are mechanically heterogeneous, yet how this shapes transport, clogging, and rheology in confined environments remains unclear. We combine microfluidic microchannel experiments with dissipative particle dynamics (DPD) simulations to study how reticulocyte morphology, deformability, and cell-cell hydrodynamic coupling govern microconfined blood flow, and link these to acute and chronic mountain sickness. Reticulocyte-rich samples show three subtypes (multilobular, cup-shaped, near-discocytic), parameterized (R1-R3) by fitting microchannel transit and shape-under-flow data. Single-cell simulations show that 5-micron microchannels amplify mechanical heterogeneity (R1 transits 30-50% more slowly than softer cells), whereas bending-dominated splenic slits discriminate subtypes by only 10-20%. Pairwise simulations show that a leading cell never lets a follower pass below its own single-cell threshold - so the order-of-magnitude, wake-"unjamming" reduction is absent - but the leader's compliance shapes crowded single-file passage: a soft reticulocyte leader lowers a trailing stiff cell's critical passage pressure by ~12% relative to a stiff (sickle-trait) leader and speeds its transit by ~10%. The controlling variable is the single-cell critical pressure gradient Delta_P_c, which rises monotonically with membrane stiffness from control discocytes through reticulocytes to sickle-cell-trait cells. Our simulations reproduce the shear-thinning viscosity of control blood, against which the reported chronic-mountain-sickness hyperviscosity reflects predominantly hematocrit-driven crowding rather than a change in single-cell rheology. These results place benign acclimatization, chronic-mountain-sickness hyperviscosity, and sickle-cell-trait splenic syndrome on a single mechanical axis defined by Delta_P_c relative to the splenic operating pressure.

Source: arXiv:2607.21810v1 - http://arxiv.org/abs/2607.21810v1 PDF: https://arxiv.org/pdf/2607.21810v1 Original Link: http://arxiv.org/abs/2607.21810v1