Ischemia leading to heart attacks and strokes is the major cause of deaths in the world. Whether an occlusion occurs or not, depends on the ability of a growing thrombus to resist forces exerted on its structure. This manuscript provides the first known in vivo measurement of the stresses that clots can withstand, before yielding to the surrounding blood flow. Namely, Lattice-Boltzmann Method flow simulations are performed based on 3D clot geometries. The latter are estimated from intravital microscopy images of laser-induced injuries in cremaster microvasculature of live mice. In addition to reporting the blood clot yield stresses, we also show that the thrombus "core" does not experience significant deformation, while its "shell" does. This indicates that the latter is more prone to embolization. Hence, drugs should be designed to target the shell selectively, while leaving the core intact (to minimize excessive bleeding). Finally, we laid down a foundation for a nondimensionalization procedure, which unraveled a relationship between clot mechanics and biology. Hence, the proposed framework could ultimately lead to a unified theory of thrombogenesis, capable of explaining all clotting events. Thus, the findings presented herein will be beneficial to the understanding and treatment of heart attacks, strokes and hemophilia.
Directed fibroblast migration is central to highly proliferative processes in regenerative medicine and developmental biology, such as wound healing and embryogenesis. However, the mechanisms by which single fibroblasts affect each other's directional decisions, while chemotaxing in microscopic tissue pores, are not well understood. Therefore, we explored the effects of two types of relevant social interactions on fibroblast PDGF-BB-induced migration in microfluidic tissue-mimicking mazes: cell sequence and mitosis. Surprisingly, it was found that in both cases, the cells display behavior that is contradictory to the chemoattractant gradient established in the maze. In case of the sequence, the cells do not like to take the same path through the maze as their predecessor, when faced with a bifurcation. To the contrary, they tend to alternate -if a leading cell takes the shorter (steeper gradient) path, the cell following it chooses the longer (weaker gradient) path, and vice versa. Additionally, we found that when a mother cell divides, its two daughters go in opposite directions (even if it means migrating against the chemoattractant gradient and overcoming on-going cell traffic). Therefore, it is apparent that fibroblasts modify each other's directional decisions in a manner that is counter-intuitive to what is expected from classical chemotaxis theory.Consequently, accounting for these effects could lead to a better understanding of tissue generation in vivo, and result in more advanced engineered tissue products in vitro.
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