Session D5: General Bio Fluids I

Modeling Shear Induced Von Willebrand Factor Binding to Collagen

Von Willebrand factor (vWF) is a blood glycoprotein that binds with platelets and collagen on injured vessel surfaces to form clots. VWF bioactivity is shear flow induced: at low shear, binding between VWF and other biological entities is suppressed; for high shear rate conditions – as are found near arterial injury sites – VWF elongates, activating its binding with platelets and collagen. Based on parameters derived from single molecule force spectroscopy experiments, we developed a coarse-grain molecular model to simulate bond formation probability as a function of shear rate. By introducing a binding criterion that depends on the conformation of a sub-monomer molecular feature of our model, the model predicts shear-induced binding, even for conditions where binding is highly energetically favorable. We further investigate the influence of various model parameters on the ability to predict shear-induced binding (vWF length, collagen site density and distribution, binding energy landscape, and slip/catch bond length) and demonstrate parameter ranges where the model provides good agreement with existing experimental data. Our results may be important for understanding vWF activity and also for achieving targeted drug therapy via biomimetic synthetic molecules.   

Universal timescales in the rheology of spheroid cell aggregates

The rheological properties of tissue play important roles in key biological processes including embryogenesis, cancer metastasis, and wound healing. Spheroid cell aggregate is a particularly interesting model system for the study of these phenomena. In the long time, they behave like drops with a surface tension. In the short, viscoelasticity also needs to be considered. In this work, we discover two coupled and universal timescales for spheroid aggregates. A total of 12 aggregate types (total aggregate number n$=$290) derived from L and GBM (glioblastoma multiforme) cells are studied with microtensiometer to obtain their surface tension. They are also allowed to relax upon release of the compression forces. The two timescales are observed during the relaxation process; their values do not depend on compression time nor the degree of deformation, and are consistent among all 12 types. Following prior work (Yu et al., Phys. Rev. Lett., 115:128303; Liu et al., J. Mech. Phys. Solids, 98:309-329) we use a rigorous mathematical theory to interpret the results, which reveals intriguing properties of the aggregates on both tissue and cellular levels. The mechanics of multicellular organization reflects both complexity and regularity due to strong active regulation.   

Impact of Inflow Conditions on Coherent Structures in an Aneurysm

An aneurysm is an enlargement of a weakened arterial wall that can be debilitating or fatal on rupture. Studies have shown that hemodynamics is integral to developing an understanding of aneurysm formation, growth, and rupture. This investigation focuses on a comprehensive study of the impact of varying inflow conditions and aneurysm shapes on spatial and temporal behavior of flow parameters and structures in an aneurysm. Two different shapes of an idealized rigid aneurysm model were studied and the non-dimensional frequency and Reynolds number were varied between 2-5 and 50-250, respectively. A ViVitro Labs SuperPump system was used to precisely control inflow conditions. Particle Image Velocimetry (PIV) measurements were performed at three different locations inside the aneurysm sac to obtain detailed velocity flow field information. The results of this study showed that aneurysm morphology significantly impacts spatial and temporal behavior of large-scale flow structures as well as wall shear stress distribution. The flow behavior and structures showed a significant difference with change in inflow conditions. A primary fluctuating flow structure was observed for Reynolds number of 50, while for higher Reynolds numbers, primary and secondary flow structures were observed. Furthermore, the paths of these coherent structures were dependent on aneurysm shape and inflow parameters.   

Impacts of coronary artery eccentricity on macro-recirculation and pressure drops using computational fluid dynamics

Coronary artery disease remains a major cause of mortality in developed countries, and is most often due to a localized flow-limiting stenosis, or narrowing, of coronary arteries. Patients often undergo invasive procedures such as X-ray angiography and fractional flow reserve to diagnose flow-limiting lesions. Even though such diagnostic techniques are well-developed, the effects of diseased coronary segments on local flow are still poorly understood. Therefore, this study investigated the effect of irregular geometries of diseased coronary segments on the macro-recirculation and local pressure minimum regions. We employed an idealized coronary artery model with a diameter of stenosis of 75{\%}. By systematically adjusting the eccentricity and the asymmetry of the coronary stenosis, we uncovered an increase in macro-recirculation size. Most importantly, the presence of this macro-recirculation signifies a local pressure minimum (identified by $\lambda_{\mathrm{2}}$ vortex identification method). This local pressure minimum has a profound effect on the pressure drops in both longitudinal and planar directions, which has implications for diagnosis and treatment of coronary artery disease.   

Simulations in Agreement With Experiments Confirm That Blood Plasma Exhibits A Pronounced Viscoelastic Behavior.

Blood plasma is a dilute aquatic solution that contains proteins and hormones such as fibrinogen, cholesterol, etc. Many studies have assumed that it behaves rheologically like a Newtonian fluid. However, more recent experimental observations (Brust et al., 2013) suggest that it exhibits significant viscoelastic effects. Understanding plasma's rheology is of crucial importance as it is well-known that deviations of plasma's shear viscosity from physiological values can indicate serious diseases. In addition, the viscoelastic character of the blood solvent should be taken into consideration as it can have a great impact on hemodynamics, especially in very narrow or stenotic microvessels. We investigate the capability of e-PTT model, which is a widely used constitutive model for macromolecular solutions, to predict inhomogeneous flows of plasma in 1) a capillary breakup extensional rheometer (CABER), using a 2D axisymmetric model and 2) a microfluidic contraction-expansion device, solving the full 3D transient governing equations. Although we use a single-mode approximation, the results are in very good agreement with the experiments, because they predict important features of blood plasma's flow, such as the bead-on-a-string formation in CABER and elongational thinning in the 3D flow.   

A sliding-control switch stabilizes synchronized states in a model of actuated cilia.

A key function of cilia, flexible hairlike appendages located on the surface of a cell, is the transport of mucus in the lungs, where the cilia self-organize forming a metachronal wave that propels the surrounding fluid. Cilia also play an important role in the locomotion of ciliated microswimmers and other biological processes. To analyze the coordinated movement of cilia interacting through a fluid, we model each cilium as an elastic, actuated body whose beat pattern is driven by a geometric switch that drives the motion of the power and recovery strokes. The cilia are coupled to the viscous fluid using a numerical method based upon a centerline distribution of regularized Stokeslets. We first characterize the beat cycle and flow produced by a single cilium and then present results on the synchronization states between two cilia that show that the in-phase equilibrium is unstable while the anti-phase equilibrium is stable under the geometric switch model. Adding a sliding-control switching mechanism stabilizes the in-phase motion.   

Acceleration induced water removal from ear canals.

Children and adults commonly experience having water trapped in the ear canals after swimming. To remove the water, individuals will shake their head sideways. Since a child's ear canal has a smaller diameter, it requires more acceleration of the head to remove the trapped water. In this study, we theoretically and experimentally investigated the acceleration required to break the surface meniscus of the water in artificial ear canals and hydrophobic-coated glass tubes. In experiments, ear canal models were 3D-printed from a CT-scanned human head. Also, glass tubes were coated with silane to match the hydrophobicity in ear canals. Then, using a linear stage, we measured the acceleration values required to forcefully eject the water from the artificial ear canals and glass tubes. A theoretical model was developed to predict the critical acceleration at a given tube diameter and water volume by using a modified Rayleigh-Taylor instability. Furthermore, this research can shed light on the potential of long-term brain injury and damage by shaking the head to push the water out of the ear canal.   

Fluid and particle transport of a hairy structure

Hairy appendages of animals are used to capture particles, sense surrounding flow, and generate propulsive force. Due to the small size of the hairy structures, their hydrodynamics have been studied mostly in very low Reynolds number. In this work, in a broad range of Reynolds number, $O$(1) $-$ $O$(100), flow structure and inertial particle dynamics around an array of two-dimensional cylinders are investigated numerically by using an immersed boundary method. Given flow fields, Maxey-Riley equation is adopted to examine particle dynamics. Here, we discuss the effects of Reynolds number, density ratio of inertial particles and fluid, and distance between cylinders on particle behaviors around a moving structure. In addition, drift volume of inertial particles is correlated with the model parameters.   

Passive object detection from pressure sensing using a 2-D viscous fluid model

Embedded pressure sensors have the ability to inform an object about the surrounding flow environment. Fish demonstrate this ability through the use of their lateral line system, which enables complex behaviors (feeding, schooling, etc.) based on measures of pressure on the surface of the body. Previous work has shown that inviscid models may be used for identifying object shapes or local flow structures based on several measurements of pressure, though these models fail to capture flow structures with large viscous effects or complex object shapes. In the present study, 2-D simulations are performed for a NACA 0012 foil passing by an object on a wall. The simulations vary object shape and size, demonstrating distinct wake behavior through pressure. A classifier is developed based on the pressure time histories in order to classify object shape and size, and demonstrated to work well using under-resolved simulated data. Experiments are also performed for a subset of object shapes and sizes. The experiments include physical sources of noise such as free surface disturbances and electrical noise to demonstrate the feasibility of this object recognition process. The classifier is tested against the physical measurements and compared with the simulated results.   

Investigations of lymphatic drainage from the interstitial space

The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.