Session ZC08: Biofluids: General III

Effects of particle shape and receptor properties on clathrin-mediated endocytosis of ligand-coated bioparticles

The membrane wrapping and internalization of ligand-coated bioparticles, such as viruses and drug carriers, through clathrin-mediated endocytosis (CME) are vitally important for intracellular transport. During CME, the shape of the particle and receptor protperties plays important roles in determination of particle-membrane interactions, but much of the previous work has been focused on spherical particles and the receptor properties have been less studied due to the oversimplifications of the models. In this work, we develop and implement a stochastic model to study the CME of particles with different shapes, and investigate the effects of mechanical (receptor flexure), geometrical (receptor length) and biochemical (ligand-receptor cutoff) properties of receptors on CME. Our results show that particles can be internalized through different entry modes depending on the particle shape. The receptor flexural rigidity plays important roles in CME. There is a threshold beyond which particle internalization will not occur. Shorter receptor length and longer ligand-receptor reaction cutoff promote formation of ligand-receptor bonds and facilitate particle internalization. Our model and simulations provide critical mechanistic insights on CME, and represents a powerful platform for guiding the design of nanoparticles for drug delivery applications.   

Correlating circulating tumor cells (CTCs) types with membrane viscoelasticity with atomic force microscopy

Atomic force microscopy (AFM) can measure the local cell membrane viscoelasticity of live CTCs by nano-indentations. Anecdotal observations suggest metastasized tumor cells bear phenotypical signatures in their membrane characteristics. Here, building on past work to detect and characterize CTC through a narrow passage by nano-strain interferometry, we have developed a mathematical framework to quantify cell membrane viscoelasticity by performing Ting's integral over force-distance measurements to differentiate cancer phenotypes. Five cell lines, prostate carcinoma (LNCap), adenocarcinoma (PC-3), breast carcinoma (T-47D), adenocarcinoma (MDA-MB-231), and lung carcinoma (A549) are used for this study. Differing from past studies, we probe the membrane with varying indentation depths to introduce elastic and plastic deformations. Results show distinctive hysteresis between the loading and unloading of different CTCs. It is also found that the multi-power law model is more suitable for cancer characterization. These viscoelastic measurements are used as boundary conditions in numerical simulation to study cell-flow-wall interactions in confinement.   

Computational simulation of the intracellular pressure response to action potentials using the permeation flux model for multicomponent electrolyte solutions

Action potentials on axons are caused by the permeation of sodium and potassium ions through each ion channel, and water molecules also pass through the channels with ions. Although the Hodgkin-Huxley model[1] explains the electric properties of the axon membrane associated with the permeation of ions, their model neglects the effect of water permeation flux on the transport phenomena. Thus, this study develops a new permeation flux model taking into account the transportations of sodium ion, potassium ion, and water. For this purpose, a novel model is proposed for the relations of each coupling permeability coefficient by focusing on the structure of the ion channel, and the proposed model is implemented into the 2-D simulation. In the simulation, the typical response of intracellular pressure to the action potential is reproduced, and the time-response profiles show reasonable agreement to the experimental results by Tasaki et al.[2]. The simulation results indicates the controllability of the pressure response by the parameter of the ratio of the molar fluxes of water and ions in the ion channel, which further suggests the possibility that the water permeation flux caused by the action potential induces the variation of the intracellular pressure. In the presentation, we show that the parameter also provides a new insight into the lag between the time developments of the action potential and the pressure response.   

Vortex dynamics within an idealized abdominal aortic aneurysm manifesting a stenosed angulated neck

Abdominal aortic aneurysm is a medical condition where the wall of the human aorta weakens as it dilates and can ultimately prove to be fatal. It is initially caused by pulsatile hemodynamic wall loading and is further aggravated by time-dependent displacement of flow structures within the aorta. The modified flow field increases the severity of wall loading, thus coupling the flow field with wall deformation. The details of the flow structures are strongly dependent on the three-dimensional flow space. The present study considers a symmetric aneurysm with an angulated stenosed neck on the inlet side and bent towards the left. On the outflow section, the bulged portion bifurcates into two branches. It is a variation of a simpler geometry, studied by the authors earlier. The spatio-temporal evolution of vortex structures in the three-dimensional geometry is studied at the flow frequency (f = 1.2 - 2.4 Hz) over a range of Reynolds numbers (Re_peak = 334 - 1192). Experiments have been conducted in a flow loop using particle image velocimetry and comparable 3D pulsatile flow simulations performed using the ANSYS-Fluent 22.1 software. With increasing Reynolds number, the vortex in the bulge shifts from one side of the wall to the other, aligning with the bend on the inflow section.  The position of the vortex greatly impacts regions of low and high wall shear stress, weakening the arterial wall. Wall loading is significantly higher when the inflow geometry is bent while comparing it against a straight model. Inflow asymmetry also impacts flow distribution in the branches of the bifurcation.   

Influence of fluid viscosity on elastocapillary coiling

A typical spider web is composed of different types of silk, each with a specific purpose. The capture thread is a soft, extensible silk decorated with sticky glue droplets, which capture prey. Elastocapillary interactions cause the silk thread to buckle and then coil within the glue droplets as the thread is compressed. The surface tension of the droplets pulls on the fiber, keeping it taut. This means that a capture thread decorated with glue droplets can be compressed and remain taut, far beyond the length at which an uncoated fiber would begin to sag. It is hypothesized that this feature evolved to prevent the web from tangling with itself during wind loading or insect impact. We expand upon previous studies by exploring the effects of droplet viscosity on the dynamic response of the drop on the fiber system. We use a model system composed of polymer fiber and silicone oil droplets and measure the sub-micro newton tension in the thread during coiling using micropipette force sensing. The results of this study provide a deeper understanding of how spider webs work and could be used to create solid-liquid hybrid metamaterials.   

Numerical study on vortex-induced vibration of undulatory seal whiskers, part I: single degree of freedom

Seal whiskers are extraordinary hydrodynamic sensors with surface geometry specialized through evolution. However, it is not well understood what information is used by the seals for sensing. To answer this question, it is important to investigate the vortex-induced vibration (VIV) of whiskers systematically. In part I of this study, the single degree-of-freedom (cross flow) VIV of a harbor seal whisker is solved using direct numerical simulation for parametrically varied reduced velocity and angle of attack (AOA) at a constant Reynolds number of 300. The whisker is modeled as a rigid body with a mass ratio of 1 and a damping ratio of 0.02. Only one segment of the undulatory shape is considered by utilizing periodic boundary conditions. At 0° AOA, the wake is characterized by the hairpin vortices and the whisker shows a typical forced vibration response despite extremely low amplitude. At 15° AOA, in addition to the hairpin vortices, a Karman-like vortex shedding is introduced near the nodal plane at a higher frequency. The VIV amplitude is modulated at the beat frequency of these two modes. As the AOA further increases, the VIV amplitude increases significantly and lock-in regions appear. An infinite branch, where the VIV persists regardless of reduced velocity, is observed for AOAs greater than 60°.   

Numerical analysis of suspension rheology of red blood cells under oscillatory shear flow

We present a numerical analysis of the rheology of a suspension of red blood cells (RBCs) for different volume fractions in a wall-bounded, effectively inertialess, small amplitude oscillatory shear (SAOS) flow for a wide range of applied frequencies. The RBCs are modeled as biconcave capsules, whose membrane is an isotropic and hyperelastic material following the Skalak constitutive law. The frequency-dependent viscoelasticity in the bulk suspension is quantified by the complex viscosity, defined by the amplitude of the particle shear stress and the phase difference between the stress and shear. Our numerical results show that the deformations of RBCs weakly depend on the shear frequency, and the normal stress differences, the membrane tension and the amplitude of the shear stress are reduced by the oscillations. The frequency-dependent complex viscosity is nevertheless partially consistent with the classical behaviour of non-Newtonian fluids, where the real part of the complex viscosity η' decreases as the frequency increases, and the imaginary part η" exhibits a maximum value at an intermediate frequency. Such local maximum frequency is the same in both dense and dilute conditions. The effect of the viscosity ratio between the cytoplasm and plasma and of the capillary number are also assessed.   

The detailed structure of the bioconvection spot: the cell-cluster radiation from single sinking region

The present study focuses on convective flows that appear in Euglena suspensions. Euglena is one of the photosynthetic microorganisms that can alter their locomotion in response to light. It moves towards regions with suitable light intensity and away from too strong light, a behavior known as positive/negative phototaxis. When Euglena suspensions are illuminated from below by strong light, the cell density in the top layer of the suspension becomes higher than that near the bottom due to their negative phototaxis. In this situation, the Rayleigh-Taylor instability occurs. The balance between the upward movement and the downward flow generates a convective flow, called “bioconvection.”

We demonstrated that a single convection cell of Euglena can exist without surrounding convection cells, which is reproducible by the experimental system controlling spatial and temporal light distributions to manipulate the local cell density of the suspension. We termed this single convection cell the “bioconvection spot.” The structure of the bioconvection spot consists of central region with high cell density and surrounding region where clusters of the individuals are radiated periodically.

The structure details and their dependency on the conditions, e.g. the suspension height and the mean cell density, remain unclear. In this presentation, we report the details of the structure including the radiation details. In particular, the bioconvection spot emits more clusters when the height and the density increase.   

A new look at scaling of samara flight

Winged, autorotating seeds from the genus Acer, have been the subject of study for botanists and aerodynamicists for decades. Despite the attention given to samaras by scientists and the relative simplicity of these winged seeds, there are still significant gaps in our understanding of how samara dynamics are informed by their physiological features. Additionally, questions remain regarding the robustness of their dynamics to physiological alterations such as mass addition by moisture or damage. In this talk, we further explore samara dynamics by applying a classical aerodynamic model to determine additional correlations. We augment seed mass and wing area and measure corresponding alterations to their descent velocity and rotation rate, thereby probing their inherent robustness to environmental perturbations. We find seeds can withstand up to a 200% increase in mass before they are unable to autorotate.   

Flow dynamics generated by a soft-robotic coral.

Xeniid corals display intriguing behavior characterized by the pulsing of their tentacles. Unlike most animals, these corals exhibit active motion for purposes other than locomotion. Inspired by these animals, we fabricate a soft-robotic coral that mimics the behavior of the corals. We conduct 3D mesurements on the active flows generated by the pulsing of the tentacles of the robot. A novel high-speed two-color scanning volumetric laser-induced fluorescence (H2C-SVLIF) imaging technique is employed to collect particle tracking velocimetry (PTV) data. The collected PTV data is utilized to reconsctruct essential flow quantities such as the velocity field and vorticity field.