Paula A. Vasquez

Rheology and spatially resolved structure of cetyltrimethylammonium bromide wormlike micelles through the shear banding transition

We present the first combined study of spatially resolved structure and shear rheology for a model shear banding fluid comprised of cetyltrimethylammonium bromide wormlike micelles. Combining conventional rheometry, velocimetry, flow birefringence, and flow-small angle neutron scattering (flow-SANS) in the 1–2 (flow-gradient) plane of shear completely characterizes shear banding in the system and enables comparison of local flow kinematics to local segmental orientation and alignment within the bands. The Giesekus constitutive equation with stress diffusion is shown to successfully model the viscoelasticity, steady shear viscosity, and shear banding kinematics. Flow-SANS measurements in the 1–2 plane exhibit a critical alignment and orientation required for shear banding, followed by a first order orientational transition to a paranematic state in the high-shear band. Master curves of the segmental orientation and alignment are constructed by comparing the local structural features to the locally observed...

A Biophysical Basis for Mucus Solids Concentration as a Candidate Biomarker for Airways Disease

In human airways diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), host defense is compromised and airways inflammation and infection often result. Mucus clearance and trapping of inhaled pathogens constitute key elements of host defense. Clearance rates are governed by mucus viscous and elastic moduli at physiological driving frequencies, whereas transport of trapped pathogens in mucus layers is governed by diffusivity. There is a clear need for simple and effective clinical biomarkers of airways disease that correlate with these properties. We tested the hypothesis that mucus solids concentration, indexed as weight percent solids (wt%), is such a biomarker. Passive microbead rheology was employed to determine both diffusive and viscoelastic properties of mucus harvested from human bronchial epithelial (HBE) cultures. Guided by sputum from healthy (1.5–2.5 wt%) and diseased (COPD, CF; 5 wt%) subjects, mucus samples were generated in vitro to mimic in vivo physiology, including intermediate range wt% to represent disease progression. Analyses of microbead datasets showed mucus diffusive properties and viscoelastic moduli scale robustly with wt%. Importantly, prominent changes in both biophysical properties arose at ∼4 wt%, consistent with a gel transition (from a more viscous-dominated solution to a more elastic-dominated gel). These findings have significant implications for: (1) penetration of cilia into the mucus layer and effectiveness of mucus transport; and (2) diffusion vs. immobilization of micro-scale particles relevant to mucus barrier properties. These data provide compelling evidence for mucus solids concentration as a baseline clinical biomarker of mucus barrier and clearance functions.

Modeling the inhomogeneous response and formation of shear bands in steady and transient flows of entangled liquids

We simulate the spatial and temporal evolution of inhomogeneous flow fields in viscometric devices such as cylindrical Couette cells. The computations focus on a class of two species elastic network models which are prototypes for a model which can capture, in a self-consistent manner, the creation and destruction of elastically active network segments as well as diffusive coupling between the microstructural conformations and the local state of stress in regions with large spatial gradients of local deformation. For each of these models, the “flow curve” of stress and apparent shear rate resulting from an assumption of homogeneous deformation is nonmonotonic and linear stability analysis shows that the region of nonmonotonic response is unstable. Steady state calculations of the full inhomogeneous flow field lead to localized shear bands that grow linearly in extent across the gap as the apparent shear rate is incremented. Time-dependent calculations in step strain experiments and in start up of steady s...

Centromere tethering confines chromosome domains.

The organization of chromosomes into territories plays an important role in a wide range of cellular processes, including gene expression, transcription, and DNA repair. Current understanding has largely excluded the spatiotemporal dynamic fluctuations of the chromatin polymer. We combine in vivo chromatin motion analysis with mathematical modeling to elucidate the physical properties that underlie the formation and fluctuations of territories. Chromosome motion varies in predicted ways along the length of the chromosome, dependent on tethering at the centromere. Detachment of a tether upon inactivation of the centromere results in increased spatial mobility. A confined bead-spring chain tethered at both ends provides a mechanism to generate observed variations in local mobility as a function of distance from the tether. These predictions are realized in experimentally determined higher effective spring constants closer to the centromere. The dynamic fluctuations and territorial organization of chromosomes are, in part, dictated by tethering at the centromere.

Microstructure and shear rheology of entangled wormlike micelles in solution

The shear rheology of a model wormlike micellar solution exhibits moderate shear thinning and curved flow velocity profiles without discontinuity (nonbanding case). The shear rheology and the flow kinematics are analyzed within the framework of the Giesekus constitutive equation. Macroscopically, the steady state flow curve of the solution exhibits shear thinning with a shear exponent <1 without hysteresis, indicative of a sample that does not shear band. The microstructure of the micellar network is probed by the combination of dynamic rheology, rheo-optics, and SANS. Flow kinematics in a Couette geometry are measured by particle tracking velocimetry and found to be consistent with predictions of the Giesekus constitutive equation fit to the bulk shear rheology. 1-2 plane SANS measurements of the segmental alignment under shear are also found to be in agreement with predictions of the constitutive equation, providing a coherent picture of the mechanisms by which wormlike micelles flow and shear thin. The...

Pericentric chromatin loops function as a nonlinear spring in mitotic force balance

During mitosis, cohesin- and condensin-based pericentric chromatin loops function as a spring network to balance spindle microtubule force.

Wormlike micellar solutions: II. Comparison between experimental data and scission model predictions

Although many constitutive models for wormlike micellar solutions have been proposed, few quantitative comparisons have been made with detailed rheological measurements. The majority of comparative studies focus on the linear viscoelastic properties of micellar solutions, which are well described by monoexponential Maxwell-like behavior. In the present work we compare the predictions of a prototypical two-species reptation-reaction model [developed in Part 1, Vasquez et al., “A network scission model for wormlike micellar solutions: I. Model formulation and viscometric flow predictions,” J. Non-Newtonian Fluid Mech. 144(2–3), 122–139 (2007)] with rheological measurements performed using a concentrated cetyl pyridinium chloride/sodium salicylate (CPyCl/NaSal) solution in a range of steady and transient shear flows. The model captures the continuous rupture and reformation of the long entangled chains that form a physically entangled viscoelastic network and the enhanced breakage rates that occur during imp...

Multi-scale kinetics of a field-directed colloidal phase transition

Polarizable colloids are expected to form crystalline equilibrium phases when exposed to a steady, uniform field. However, when colloids become localized this field-induced phase transition arrests and the suspension persists indefinitely as a kinetically trapped, percolated structure. We anneal such gels formed from magneto-rheological fluids by toggling the field strength at varied frequencies. This processing allows the arrested structure to relax periodically to equilibrium—colloid-rich, cylindrical columns. Two distinct growth regimes are observed: one in which particle domains ripen through diffusive relaxation of the gel, and the other where the system-spanning structure collapses and columnar domains coalesce apparently through field-driven interactions. There is a stark boundary as a function of magnetic field strength and toggle frequency distinguishing the two regimes. These results demonstrate how kinetic barriers to a colloidal phase transition are subverted through measured, periodic variation of driving forces. Such directed assembly may be harnessed to create unique materials from dispersions of colloids.

DNA loops generate intracentromere tension in mitosis

The geometry and arrangement of DNA loops in the pericentric region of the budding yeast centromere create a DNA-based molecular shock absorber that serves as the basis for how tension is generated between sister centromeres in mitosis.

Individual pericentromeres display coordinated motion and stretching in the yeast spindle

During mitosis, cohesin and condensin cross-link pericentromeres of different chromosomes to coordinate centromere attachment sites.