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  1. Abstract

    Countless biophysical studies have sought distinct markers in the cellular mechanical response that could be linked to morphogenesis, homeostasis, and disease. Here, an iterative-fitting methodology visualizes the time-dependent viscoelastic behavior of human skin cells under physiologically relevant conditions. Past investigations often involved parameterizing elastic relationships and assuming purely Hertzian contact mechanics, which fails to properly account for the rich temporal information available. We demonstrate the performance superiority of the proposed iterative viscoelastic characterization method over standard open-search approaches. Our viscoelastic measurements revealed that 2D adherent metastatic melanoma cells exhibit reduced elasticity compared to their normal counterparts—melanocytes and fibroblasts, and are significantly less viscous than fibroblasts over timescales spanning three orders of magnitude. The measured loss angle indicates clear differential viscoelastic responses across multiple timescales between the measured cells. This method provides insight into the complex viscoelastic behavior of metastatic melanoma cells relevant to better understanding cancer metastasis and aggression.

     
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  2. Shear-induced pair interactions between viscous drops suspended in a viscoelastic matrix are numerically investigated examining the effects of elasticity and drop deformability on their post-collision trajectory. Two different trajectory types are identified depending on the Weissenberg number Wi and capillary number Ca. Drops suspended in a Newtonian matrix ( Wi =  0.0) show a passing trajectory where drops slide past each other and separate in the stream-wise direction. However, when increasing the Weissenberg number above a critical value, a tumbling/doublet trajectory is observed where two drops rotate around the midpoint of the line joining their centers, as was also seen previously for rigid particles. The tumbling trajectory is explained by investigating the flow around a single drop in shear. Elasticity generates a larger region of spiraling streamlines around a drop, which, during a pair interaction, traps the second drop giving rise to the tumbling pair. Decreasing deformability (lower Ca) and increasing viscoelasticity (higher Wi) favor a tumbling trajectory. With simulations sweeping the parameter space, we obtain a phase plot of the two different trajectories as functions of Ca and Wi. Treating the tension along the curved streamlines due to the non-zero first normal stress difference in the viscoelastic medium as an enhancement to the interfacial tension, we have developed an approximate force balance model for the zone of spiraling streamlines. It qualitatively captures the observed scaling of the critical Ca and Wi values at the phase boundary. The effects of unequal size, initial configuration, and non-unity viscosity ratio are briefly investigated.

     
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  3. Hydrodynamic interactions generate a diffusive motion in particulates in a shear flow, which plays seminal roles in overall particulate rheology and its microstructure. Here we investigate the shear induced diffusion in a red-blood cell (RBC) suspension using a numerical simulation resolving individual motion and deformation of RBCs. The non-spherical resting shape of RBCs gives rise to qualitatively different regimes of cell dynamics in a shear flow such as tank-treading, breathing, tumbling and swinging, depending on the cell flexibility determined by the elastic capillary number. We show that the transition from tumbling to tank-treading causes a reduction in the gradient diffusivity. The diffusivity is computed using a continuum approach from the evolution of a randomly packed cell-layer width with time as well as by the dynamic structure factor of the suspension. Both approaches, although operationally different, match and show that for intermediate capillary numbers RBCs cease tumbling accompanied by a drop in the coefficient of gradient diffusivity. A further increase of capillary number increases the diffusivity due to increased deformation. The effects of bending modulus and viscosity ratio variations are also briefly investigated. The computed shear induced diffusivity was compared with values in the literature. Apart from its effects in margination of cells in blood flow and use in medical diagnostics, the phenomenon broadly offers important insights into suspensions of deformable particles with non-spherical equilibrium shapes, which also could play a critical role in using particle flexibility for applications such as label free separation or material processing. 
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