The viscosity of blood has long been used as an indicator in the understanding and treatment of disease, and the advent of modern viscometers allows its measurement with ever-improving clinical convenience. However, these advances have not been matched by theoretical developments that can yield a quantitative understanding of blood’s microrheology and its possible connection to relevant biomolecules (e.g., fibrinogen). Using coarse-grained molecular dynamics and two different red blood cell models, we accurately predict the dependence of blood viscosity on shear rate and hematocrit. We explicitly represent cell–cell interactions and identify the types and sizes of reversible rouleaux structures that yield a tremendous increase of blood viscosity at low shear rates. We also present the first quantitative estimates of the magnitude of adhesive forces between red cells. In addition, our simulations support the hypothesis, previously deduced from experiments, of yield stress as an indicator of cell aggregation. This non-Newtonian behavior is analyzed and related to the suspension’s microstructure, deformation, and dynamics of single red blood cells. The most complex cell dynamics occurs in the intermediate shear rate regime, where individual cells experience severe deformation and transient folded conformations. The generality of these cell models together with single-cell measurements points to the future prediction of blood-viscosity anomalies and the corresponding microstructures associated with various diseases (e.g., malaria, AIDS, and diabetes mellitus). The models can easily be adapted to tune the properties of a much wider class of complex fluids including capsule and vesicle suspensions.

Drug delivery by micro- and nano-carriers enables controlled transport of pharmaceuticals to targeted sites. Even though carrier fabrication has made much progress recently, the delivery including controlled particle distribution and adhesion within the body remains a great challenge. The adhesion of carriers is strongly affected by their margination properties (migration toward walls) in the microvasculature. To investigate margination characteristics of carriers of different shapes and sizes and to elucidate the relevant physical mechanisms, we employ mesoscopic hydrodynamic simulations of blood flow. Particle margination is studied for a wide range of hematocrit values, vessel sizes and flow rates, using two- and three-dimensional models. The simulations show that the margination properties of particles improve with increasing carrier size. Spherical particles yield slightly better margination than ellipsoidal carriers; however, ellipsoidal particles exhibit a slower rotational dynamics near a wall favoring their adhesion. In conclusion, micron-sized ellipsoidal particles are favorable for drug delivery in comparison with sub-micron spherical particles.

Significance: Our work reveals rich RBCs’ dynamic morphologies which govern blood shear thinning under microcirculatory flow conditions, contrary to the current paradigm assuming steady RBC orientation and membrane circulation. Our results suggest that any pathological change in RBCs’ local rheology will impact the onset of these morphological transitions and should play a key role in pathological blood flow.