At the cellular scale, blood fluidity and mass transport depend on the dynamics of red blood cells in blood flow, specifically on their deformation and orientation. These dynamics are governed by cellular rheological properties, such as internal viscosity and cytoskeleton elasticity. In diseases in which cell rheology is altered genetically or by parasitic invasion or by changes in the microenvironment, blood flow may be severely impaired. The nonlinear interplay between cell rheology and flow may generate complex dynamics, which remain largely unexplored experimentally. Under simple shear flow, only two motions, "tumbling" and "tank-treading," have been described experimentally and relate to cell mechanics. Here, we elucidate the full dynamics of red blood cells in shear flow by coupling two videomicroscopy approaches providing multidirectional pictures of cells, and we analyze the mechanical origin of the observed dynamics. We show that contrary to common belief, when red blood cells flip into the flow, their orientation is determined by the shear rate. We discuss the "rolling" motion, similar to a rolling wheel. This motion, which permits the cells to avoid energetically costly deformations, is a true signature of the cytoskeleton elasticity. We highlight a hysteresis cycle and two transient dynamics driven by the shear rate: an intermittent regime during the "tank-treading-to-flipping" transition and a Frisbee-like "spinning" regime during the "rolling-to-tank-treading" transition. Finally, we reveal that the biconcave red cell shape is highly stable under moderate shear stresses, and we interpret this result in terms of stress-free shape and elastic buckling. . Its fluidity strongly depends on its behavior in flow, which is a key factor of proper tissue perfusion. At the cellular scale, blood flow behavior is affected primarily by the RBC response to the hydrodynamic stress in terms of cell orientation relative to the flow direction and of cell deformation. For example, on one hand, at low shear rates, similar cell orientations may favor the formation of stacks (rouleaux) (1) of RBCs, like rolls of coins, which increases blood viscosity. On the other hand, at high shear rates, the individualization of RBCs, their alignment, and their stretching in the flow (2) decrease blood viscosity (3). The orientation and the deformation in flow of RBCs are governed by their rheological properties. They result from the viscoelastic contributions of all components of the cell composite structure. Moreover, RBC rheological properties also depend on the microenvironment and on metabolic functionality (4). Both local and systemic disturbances of homeostasis (in diabetes mellitus, hypertension) have the potential to induce RBC rheological alterations and consequently to impair blood circulation. It therefore is crucial to understand the relationships between the rheological properties of RBCs and their orientation and deformation in flow. This question is far from trivial because even in a simple shear flow, RBCs present a v...
DNA folding and dynamics along with major nuclear functions are determined by chromosome structural properties, which remain, thus far, elusive in vivo. Here, we combine polymer modeling and single particle tracking experiments to determine the physico-chemical parameters of chromatin in vitro and in living yeast. We find that the motion of reconstituted chromatin fibers can be recapitulated by the Rouse model using mechanical parameters of nucleosome arrays deduced from structural simulations. Conversely, we report that the Rouse model shows some inconsistencies to analyze the motion and structural properties inferred from yeast chromosomes determined with chromosome conformation capture techniques (specifically, Hi-C). We hence introduce the Rouse model with Transient Internal Contacts (RouseTIC), in which random association and dissociation occurs along the chromosome contour. The parametrization of this model by fitting motion and Hi-C data allows us to measure the kinetic parameters of the contact formation reaction. Chromosome contacts appear to be transient; associated to a lifetime of seconds and characterized by an attractive energy of –0.3 to –0.5 kBT. We suggest attributing this energy to the occurrence of histone tail-DNA contacts and notice that its amplitude sets chromosomes in ‘theta’ conditions, in which they are poised for compartmentalization and phase separation.
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