Abstract The configuration of proteins is critical for their biochemical behavior. Mechanical stresses that act on them can affect their behavior leading to the development of decease. The von Willebrand factor (vWF) protein circulating with the blood loses its efficacy when it undergoes non-physiological hemodynamic stresses. While often overlooked, extensional stresses can affect the structure of vWF at much lower stress levels than shear stresses. The statistical distribution of extensional stress as it applies on models of the vWF molecule within turbulent flow was examined here. The stress on the molecules of the protein was calculated with computations that utilized a Lagrangian approach for the determination of the molecule trajectories in the flow filed. The history of the stresses on the proteins was also calculated. Two different flow fields were considered as models of typical flows in cardiovascular mechanical devises, one was a Poiseuille flow and the other was a Poiseuille–Couette flow field. The data showed that the distribution of stresses is important for the design of blood flow devices because the average stress can be below the critical value for protein damage, but tails of the distribution can be outside the critical stress regime.
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Computations of the shear stresses distribution experienced by passive particles as they circulate in turbulent flow: A case study for vWF protein molecules
The stress distribution along the trajectories of passive particles released in turbulent flow were computed with the use of Lagrangian methods and direct numerical simulations. The flow fields selected were transitional Poiseuille-Couette flow situations found in ventricular assist devices and turbulent flows at conditions found in blood pumps. The passive particle properties were selected to represent molecules of the von Willebrand factor (vWF) protein. Damage to the vWF molecule can cause disease, most often related to hemostasis. The hydrodynamic shear stresses along the trajectories of the particles were calculated and the changes in the distribution of stresses were determined for proteins released in different locations in the flow field and as a function of exposure time. The stress distributions indicated that even when the average applied stress was within a safe operating regime, the proteins spent part of their trajectories in flow areas of damaging stress. Further examination showed that the history of the distribution of stresses applied on the vWF molecules, rather than the average, should be used to evaluate hydrodynamically-induced damage.
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- Award ID(s):
- 1803014
- NSF-PAR ID:
- 10430645
- Editor(s):
- Borazjani, Iman
- Date Published:
- Journal Name:
- PLOS ONE
- Volume:
- 17
- Issue:
- 8
- ISSN:
- 1932-6203
- Page Range / eLocation ID:
- e0273312
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Background Patients with continuous flow ventricular assist devices (CF‐VADs) are at high risk for non‐surgical bleeding, speculated to associate with the loss of pulsatility following CF‐VAD placement. It has been hypothesized that continuous shear stress causes elongation and increased enzymatic degradation of von Willebrand Factor (vWF), a key player in thrombus formation at sites of vascular damage. However, the role of loss of pulsatility on the unravelling behavior of vWF has not been widely explored.
Methods vWF molecules were immobilized on the surface of microfluidic devices and subjected to various pulsatile flow profiles, including continuous flow and pulsatile flow of different magnitudes,
dQ /dt (i.e., first derivative of flow rate) of pulsatility and pulse frequencies to mimic in vivo shear flow environments with and without CF‐VAD support. VWF elongation was observed using total internal reflection fluorescence (TIRF) microscopy. Besides, the vWF level is measured from the patients’ blood sample before and after CF‐VAD implantation from a clinical perspective. To our knowledge, this work is the first in providing direct, visual observation of single vWF molecule extension under controlled‐pulsatile shear flow.Results Unravelling of vWF (total sample size
n ~ 200 molecules) is significantly reduced under pulsatile flow (p < 0.01) compared to continuous flow. An increase in the magnitude of pulsatility further reduces unravelling lengths, while lower frequency of pulsatility (20 vs. 60 pulses per min) does not have a major effect on the maximum or minimum unravelling lengths. Evaluation of CF‐VAD patient blood samples (n = 13) demonstrates that vWF levels decreased by ~40% following CF‐VAD placement (p < 0.01), which correlates to single‐molecule observations from a clinical point of view.Conclusions Pulsatile flow reduces unfolding of vWF compared to continuous flow and a lower pulse frequency of 20 pulses/minute yielded comparable vWF unfolding to 60 pulses/minute. These findings could shed light on non‐surgical bleeding associated with the loss of pulsatility following CF‐VAD placement.
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Abstract A remarkably consistent Lagrangian upwelling circulation at monthly and longer time scales is observed in a 17-yr time series of current profiles in 12 m of water on the southern New England inner shelf. The upwelling circulation is strongest in summer, with a current magnitude of ∼1 cm s −1 , which flushes the inner shelf in ∼2.5 days. The average winter upwelling circulation is about one-half of the average summer upwelling circulation, but with larger month-to-month variations driven, in part, by cross-shelf wind stresses. The persistent upwelling circulation is not wind-driven; it is driven by a cross-shelf buoyancy force associated with less-dense water near the coast. The cross-shelf density gradient is primarily due to temperature in summer, when strong surface heating warms shallower nearshore water more than deeper offshore water, and to salinity in winter, caused by fresher water near the coast. In the absence of turbulent stresses, the cross-shelf density gradient would be in a geostrophic, thermal-wind balance with the vertical shear in the along-shelf current. However, turbulent stresses over the inner shelf attributable to strong tidal currents and wind stress cause a partial breakdown of the thermal-wind balance that releases the buoyancy force, which drives the observed upwelling circulation. The presence of a cross-shelf density gradient has a profound impact on exchange across this inner shelf. Many inner shelves are characterized by turbulent stresses and cross-shelf density gradients with lighter water near the coast, suggesting turbulent thermal-wind-driven coastal upwelling may be a broadly important cross-shelf exchange mechanism. Significance Statement A remarkably consistent upwelling circulation at monthly time scales is observed in a 17-yr time series of current profiles in shallow water off southern New England. This is not the traditional wind-driven coastal upwelling; instead, it is forced by cross-shelf buoyancy (density) gradients, released by turbulent stresses in shallow water. The persistent upwelling circulation is strongest in summer, when wind and wave forcing are weak, and flushes the inner portion of the continental shelf in a few days. Consequently, this buoyancy-driven coastal upwelling is important for cooling the inner shelf and provides a reliable mechanism for cross-shelf exchange. Many inner shelves are characterized by cross-shelf density gradients and turbulent stresses, suggesting this may be a broadly important cross-shelf exchange mechanism.more » « less
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We conducted a spectral analysis of the turbulence kinetic energy (TKE) budget in a bubble plume using particle image velocimetry with fluorescent particles. Our findings confirmed the hypothesis of an inverse energy cascade in the bubble plume, where TKE is transferred from small to large eddies. This is attributed to direct injection of TKE by bubble passages across a wide range of scales, in contrast to canonical shear production of TKE in large scales. Turbulence dissipation was identified as the primary sink of the bubble-produced TKE and occurred at all scales. The decomposition of velocities using the critical length scale of inter-scale energy transfer allowed us to distinguish between large- and small-scale motions in the bubble plume. The large-scale turbulent fluctuations exhibited a skewed distribution and were likely associated with the return flow after bubble passage and the velocities induced by the bubble wake. The small-scale turbulent fluctuations followed a Gaussian distribution relatively well. The large-scale motions contributed to over half of the Reynolds stresses, while there were significant small-scale contributions to the normal stresses near the plume center but not to the shear stress. The large-scale motions in the vorticity field induced a street of vertically elongated vortex pairs, while the small-scale vortices exhibited similar sizes in both horizontal and vertical directions.
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Abstract Aerodynamic surface stress imposed by the atmospheric surface layer (ASL) drives aeolian sediment transport processes. When the imposed stress exceeds fluid threshold, splashing sand grains release fine (aerosol) particles. This process stops when the imposed stress falls below an impact threshold. Turbulence in the ASL is composed of elongated streaks of relatively high and low streamwise momentum (high‐momentum and low‐momentum regions, HMR and LMR, respectively), and these streaks are aligned with the prevailing winds. Streamwise‐wall‐normal turbulent stress is the concurrent product of fluctuations in streamwise and vertical velocity. These production mechanisms are categorized into quadrants: sweeps, inner interactions, ejections, and outer interactions, where the first two and last two occur within HMRs and LMRs, respectively. Under typical ASL conditions, the time‐averaged shear velocity is bound between 0.3 and 0.5 m/s, demonstrating the importance of fluctuations in mobilizing sand grains via saltation: time‐averaged shear velocity exceeding threshold does not correspond with typical ASL conditions. Given the aforementioned contributions to streamwise‐wall‐normal turbulent stresses from sweeps and ejections, it is self‐evident that under typical conditions only sweeps possess the momentum required to exceed threshold. But, any dust released is trapped by downwelling from aloft; ejections rarely exceed threshold, but they contain the positive vertical velocity needed to entrain. These attributes represent an entrainment paradox. Complementary field data are used to demonstrate the existence of an entrainment paradox. Large eddy simulation has been used to capture space‐time evolution of an idealized ASL and identify mechanistic flow physics central to entrainment.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1371/journal.pone.0273312
