Multicellular aggregates of circulating tumor cells (CTC clusters) are potent initiators of distant organ metastasis. However, it is currently assumed that CTC clusters are too large to pass through narrow vessels to reach these organs. Here, we present evidence that challenges this assumption through the use of microfluidic devices designed to mimic human capillary constrictions and CTC clusters obtained from patient and cancer cell origins. Over 90% of clusters containing up to 20 cells successfully traversed 5-to 10-μm constrictions even in whole blood. Clusters rapidly and reversibly reorganized into single-file chain-like geometries that substantially reduced their hydrodynamic resistances. Xenotransplantation of human CTC clusters into zebrafish showed similar reorganization and transit through capillary-sized vessels in vivo. Preliminary experiments demonstrated that clusters could be disrupted during transit using drugs that affected cellular interaction energies. These findings suggest that CTC clusters may contribute a greater role to tumor dissemination than previously believed and may point to strategies for combating CTC cluster-initiated metastasis.microfluidics | cancer metastasis | CTC clusters | circulating tumor cell cluster microemboli | capillary microhemodynamics

Rheological and morphological properties of reactively compatibilized thermoplastic olefin (TPO) blendsa) J. Rheol. 56, 625 (2012); 10.1122/1.3700966 Temperature sensitive microgel suspensions: Colloidal phase behavior and rheology of soft spheresThe flow properties of high volume fraction hard sphere colloid-polymer suspensions are studied as a function of polymer concentration, depletion attraction range, and solvent quality up to, and well beyond, the gelation boundary. As the gel boundary is approached, the shear viscosity tends to diverge in a critical power law manner at a polymer concentration that is a function of the polymer radius of gyration and solvency condition. The shear viscosity for different polymer size suspensions can be collapsed onto a master curve motivated by mode coupling theory ͑MCT͒. The low frequency elastic modulus grows rapidly with increasing depletion attraction near the gel boundary, but becomes a dramatically weaker function of polymer concentration as the gel state is more deeply entered. A simplified version of MCT with accurate, no adjustable parameter polymer reference interaction site model ͑PRISM͒ theory structural input has been applied to predict the gelation boundaries and elastic shear moduli. The calculated gel lines are in semiquantitative agreement with experiment at high volume fractions, but increasingly deviate upon particle dilution. Calculations of the dependence of the gel elastic shear moduli on particle-polymer size asymmetry and scaled polymer concentration are in excellent agreement with experiment, and deep in the gel follow a power law dependence on polymer concentration. Quantitatively, MCT-PRISM elastic moduli are higher than experiment by a nearly constant large factor. This discrepancy is suggested to be due to the heterogeneous nature of the gel structure which small angle scattering experiments show consists of dense clusters and voids of characteristic length scales ϳ4 -7 particle diameters. A simple idea for correcting the particle level MCT modulus by employing cluster network concepts is proposed.

The conformation and diffusion of a single DNA molecule confined between two parallel plates are examined using both single molecule experiments and Brownian dynamics simulations accounting for hydrodynamic interactions. The degree of chain stretching and the diffusivity are characterized as a function of the chain confinement and the channel geometry. Good agreement is found between the simulations, experiments, and scaling theory predictions.

A simplified mode-coupling theory (MCT) of ergodic-nonergodic transitions, in conjunction with an accurate two-component polymer reference interaction site model (PRISM) theory for equilibrium structural correlations, has been systematically applied to investigate gelation, localization, and elasticity of flexible polymer-hard particle suspensions. The particle volume fraction at the fluid-gel transition is predicted to depend exponentially on reduced polymer concentration and size asymmetry ratio at relatively high colloid concentrations. In contrast, at lower particle volume fractions, a power-law dependence on polymer concentration is found with effective exponents and prefactors that depend systematically on the polymer/particle size ratio. Remarkable power-law and near universal scaling behavior is found for the localization length and elastic shear modulus. Multiple experiments for gel boundaries and shear moduli are in good agreement with the no adjustable parameter theory. The one exception is the absolute magnitude of the shear modulus which is strongly overpredicted, apparently due to nonequilibrium dense cluster formation. The simplified MCT-PRISM theory also captures the qualitative aspects of the weak depletion-driven "glass melting" phenomenon at high particle volume fractions. Calculations based on an effective one-component model of structure within a low particle volume fraction framework yield qualitatively different features than the two-component approach and are apparently all in disagreement with experiments. This suggests that volume fraction and size asymmetry dependent many-body screening of polymer-mediated depletion attractions at finite particle concentrations are important.

A systematic experimental study of polymer-induced changes of the collective structure of model hard-sphere nanocolloids in the fluid and gel states has been carried out using ultra-small-angle x-ray scattering. The focus is on small, nonadsorbing polymer depletants where a direct transition from the homogeneous fluid phase to a nonequilibrium gel state occurs with increasing polymer additions. As the polymer concentration is increased in the homogeneous fluid phase, the low angle concentration fluctuations monotonically increase, the characteristic interparticle separation decreases and tends to saturate, and the intensity of the cage order peak varies in a non-monotonic manner. These equilibrium structural changes depend in a systematic fashion on colloid volume fraction and polymer-colloid size asymmetry, and are in near quantitative agreement with the parameter-free polymer reference interaction site model theory calculations. By combining the accurate equilibrium theory with experimental observations, the loss of ergodicity and nonequilibrium structure formation in the gel state can be deduced. Abrupt departures between theory and experiment on the ∼2-3 particle diameter and greater length scales are observed as the gel boundary is traversed. The liquid-like local cage structure is arrested. Intermediate scale fluctuations are suppressed suggesting the formation of small, compact clusters. Large amplitude, Porod-like fluctuations emerge on large length scales due to quenched heterogeneities which are analysed using a random two-phase composite model. By combining the results of all the scattering experiments and theoretical calculations a qualitative real space picture of the gel microstructure is constructed, and its mechanical consequences are qualitatively discussed.