A strain-based model for mechanical hemolysis based on a coarse-grained red blood cell model.

Mechanical hemolysis is a major concern in the design of cardiovascular devices, such as prosthetic heart valves and ventricular assist devices. The primary cause of mechanical hemolysis is the impact of the device on the local blood flow, which exposes blood elements to non-physiologic conditions. The majority of existing hemolysis models correlate red blood cell (RBC) damage to the imposed fluid shear stress and exposure time. Only recently more realistic, strain-based models have been proposed, where the RBC's response to the imposed hydrodynamic loading is accounted for. In the present work we extend strain-based models by introducing a high-fidelity representation of RBCs, which is based on existing coarse-grained particle dynamics approach. We report a series of numerical experiments in simple shear flows of increasing complexity, to illuminate the basic differences between existing models and establish their accuracy in comparison to the high-fidelity RBC approach. We also consider a practical configuration, where the flow through an artificial heart valve is computed. Our results shed light on the strengths and weaknesses of each approach and identify the key gaps that should be addressed in the development of new models.

Modeling of the major gas vesicle protein, GvpA: from protein sequence to vesicle wall structure.

The structure and assembly process of gas vesicles have received significant attention in recent decades, although relatively little is still known. This work combines state-of-the-art computational methods to develop a model for the major gas vesicle protein, GvpA, and explore its structure within the assembled vesicle. Elucidating this protein's structure has been challenging due to its adherent and aggregative nature, which has so far precluded in-depth biochemical analyses. Moreover, GvpA has extremely low similarity with any known protein structure, which renders homology modeling methods ineffective. Thus, alternate approaches were used to model its tertiary structure. Starting with the sequence from haloarchaeon Halobacterium sp. NRC-1, we performed ab initio modeling and threading to acquire a multitude of structure decoys, which were equilibrated and ranked using molecular dynamics and mechanics, respectively. The highest ranked predictions exhibited an α-ß-ß-α secondary structure in agreement with earlier experimental findings, as well as with our own secondary structure predictions. Afterwards, GvpA subunits were docked in a quasi-periodic arrangement to investigate the assembly of the vesicle wall and to conduct simulations of contact-mode atomic force microscopy imaging, which allowed us to reconcile the structure predictions with the available experimental data. Finally, the GvpA structure for two representative organisms, Anabaena flos-aquae and Calothrix sp. PCC 7601, was also predicted, which reproduced the major features of our GvpA model, supporting the expectation that homologous GvpA sequences synthesized by different organisms should exhibit similar structures.