We computationally study the motion of an initially spherical capsule flowing through a straight channel with an orthogonal lateral branch, using a three-dimensional immersed-boundary lattice-Boltzmann method. The capsule is enclosed by a strain-hardening membrane and contains an internal fluid of the same viscosity as the fluid in which it is suspended. Our primary focus is to study the influence of the geometry of the side branch on the capsule path selection. Specifically, we consider the case where the side branch cross-section is half that of the straight channel and study various bifurcation configurations, where the branch is rectangular or square, centred or not on the straight channel axis. The capsule is initially centred on the axis of the straight channel. We impose the flow rate split ratio between the two downstream branches of the bifurcation. We summarise the results obtained for different capsule-to-channel size ratios, flow Reynolds number $Re$ (based on the parent channel size and average flow speed) and capsule mechanical deformability (as measured by the capillary number) in phase diagrams giving the critical flow rate split ratio above which the capsule flows into the side branch. A major finding is that, at equal flow rate split between the two downstream branches, the capsule will enter a branch which is narrow in the spanwise direction, but will not enter a branch which is narrow in the flow direction. For $Re\leqslant 5$, this novel intriguing phenomenon primarily results from the background flow, which is strongly influenced by the side branch geometry. For higher values of $Re$, the capsule relative size and deformability also play specific roles in the path selection. The capsule trajectory does not always obey the classical Fung’s bifurcation law, which stipulates that a particle (in Fung’s case, a red blood cell) enters the bifurcation branch with the highest flow rate. We also consider the same branched channels operating under constant pressure drop conditions and show that such systems are difficult to control due to the transient additional pressure drop caused by the capsule. The present results obtained for dilute systems open new perspectives on the design of microfluidic systems, with optimal channel geometries and flow conditions to enrich cell and particle suspensions.
Sudden hypo-osmotic challenge increases chondrocyte mechanics by activation of RVD and interaction with the actin cytoskeleton. Moreover, the rate of hypo-osmotic challenge is shown to have a profound effect on chondrocyte morphology and biomechanics. This important phenomenon needs to be considered when studying the response of chondrocytes to pathological hypo-osmotic stress.
SummaryObjectivesPrimary cilia are microtubule based organelles which control a variety of signalling pathways important in cartilage development, health and disease. This study examines the role of the intraflagellar transport (IFT) protein, IFT88, in regulating fundamental actin organisation and mechanics in articular chondrocytes.MethodsThe study used an established chondrocyte cell line with and without hypomorphic mutation of IFT88 (IFT88orpk). Confocal microscopy was used to quantify F-actin and myosin IIB organisation. Viscoelastic cell and actin cortex mechanics were determined using micropipette aspiration with actin dynamics visualised in live cells transfected with LifeACT-GFP.ResultsIFT88orpk cells exhibited a significant increase in acto-myosin stress fibre organisation relative to wild-type (WT) cells in monolayer and an altered response to cytochalasin D. Rounded IFT88orpk cells cultured in suspension exhibited reduced cortical actin expression with reduced cellular equilibrium modulus. Micropipette aspiration resulted in reduced membrane bleb formation in IFT88orpk cells. Following membrane blebbing, IFT88orpk cells exhibited slower reformation of the actin cortex. IFT88orpk cells showed increased actin deformability and reduced cortical tension confirming that IFT regulates actin cortex mechanics. The reduced cortical tension is also consistent with the reduced bleb formation.ConclusionsThis study demonstrates for the first time that the ciliary protein IFT88 regulates fundamental actin organisation and the stiffness of the actin cortex leading to alterations in cell deformation, mechanical properties and blebbing in an IFT88 chondrocyte cell line. This adds to the growing understanding of the role of primary cilia and IFT in regulating cartilage biology.
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