Anomalous crystalline ordering of particles in a viscoelastic fluid under high shear.

Addition of particles to a viscoelastic suspension dramatically alters the properties of the mixture, particularly when it is sheared or otherwise processed. Shear-induced stretching of the polymers results in elastic stress that causes a substantial increase in measured viscosity with increasing shear, and an attractive interaction between particles, leading to their chaining. At even higher shear rates, the flow becomes unstable, even in the absence of particles. This instability makes it very difficult to determine the properties of a particle suspension. Here, we use a fully immersed parallel plate geometry to measure the high-shear-rate behavior of a suspension of particles in a viscoelastic fluid. We find an unexpected separation of the particles within the suspension resulting in the formation of a layer of particles in the center of the cell. Remarkably, monodisperse particles form a crystalline layer which dramatically alters the shear instability. By combining measurements of the velocity field and torque fluctuations, we show that this solid layer disrupts the flow instability and introduces a single-frequency component to the torque fluctuations that reflects a dominant velocity pattern in the flow. These results highlight the interplay between particles and a suspending viscoelastic fluid at very high shear rates.

Artificial intelligence velocimetry reveals in vivo flow rates, pressure gradients, and shear stresses in murine perivascular flows.

Quantifying the flow of cerebrospinal fluid (CSF) is crucial for understanding brain waste clearance and nutrient delivery, as well as edema in pathological conditions such as stroke. However, existing in vivo techniques are limited to sparse velocity measurements in pial perivascular spaces (PVSs) or low-resolution measurements from brain-wide imaging. Additionally, volume flow rate, pressure, and shear stress variation in PVSs are essentially impossible to measure in vivo. Here, we show that artificial intelligence velocimetry (AIV) can integrate sparse velocity measurements with physics-informed neural networks to quantify CSF flow in PVSs. With AIV, we infer three-dimensional (3D), high-resolution velocity, pressure, and shear stress. Validation comes from training with 70% of PTV measurements and demonstrating close agreement with the remaining 30%. A sensitivity analysis on the AIV inputs shows that the uncertainty in AIV inferred quantities due to uncertainties in the PVS boundary locations inherent to in vivo imaging is less than 30%, and the uncertainty from the neural net initialization is less than 1%. In PVSs of N = 4 wild-type mice we find mean flow speed 16.33 ± 11.09 µm/s, volume flow rate 2.22 ± 1.983 × 103 µm3/s, axial pressure gradient ( - 2.75 ± 2.01)×10-4 Pa/µm (-2.07 ± 1.51 mmHg/m), and wall shear stress (3.00 ± 1.45)×10-3 Pa (all mean ± SE). Pressure gradients, flow rates, and resistances agree with prior predictions. AIV infers in vivo PVS flows in remarkable detail, which will improve fluid dynamic models and potentially clarify how CSF flow changes with aging, Alzheimer's disease, and small vessel disease.

Insights from high-fidelity modeling of industrial rotary bell atomization.

The global automotive industry sprayed over 2.6 billion liters of paint in 2018, much of which through electrostatic rotary bell atomization, a highly complex process involving the fluid mechanics of rapidly rotating thin films tearing apart into micrometer-thin filaments and droplets. Coating operations account for 65% of the energy usage in a typical automotive assembly plant, representing 10,000s of gigawatt-hours each year in the United States alone. Optimization of these processes would allow for improved robustness, reduced material waste, increased throughput, and significantly reduced energy usage. Here, we introduce a high-fidelity mathematical and algorithmic framework to analyze rotary bell atomization dynamics at industrially relevant conditions. Our approach couples laboratory experiment with the development of robust non-Newtonian fluid models; devises high-order accurate numerical methods to compute the coupled bell, paint, and gas dynamics; and efficiently exploits high-performance supercomputing architectures. These advances have yielded insight into key dynamics, including i) parametric trends in film, sheeting, and filament characteristics as a function of fluid rheology, delivery rates, and bell speed; ii) the impact of nonuniform film thicknesses on atomization performance; and iii) an understanding of spray composition via primary and secondary atomization. These findings result in coating design principles that are poised to improve energy- and cost-efficiency in a wide array of industrial and manufacturing settings.

Structure of propagating high-stress fronts in a shear-thickening suspension.

We report direct measurements of spatially resolved stress at the boundary of a shear-thickening cornstarch suspension revealing persistent regions of high local stress propagating in the flow direction at the speed of the top boundary. The persistence of these propagating fronts enables precise measurements of their structure, including the profile of boundary stress measured by boundary stress microscopy (BSM) and the nonaffine velocity of particles at the bottom boundary of the suspension measured by particle image velocimetry (PIV). In addition, we directly measure the relative flow between the particle phase and the suspending fluid (fluid migration) and find the migration is highly localized to the fronts and changes direction across the front, indicating that the fronts are composed of a localized region of high dilatant pressure and low particle concentration. The magnitude of the flow indicates that the pore pressure difference driving the fluid migration is comparable to the critical shear stress for the onset of shear thickening. The propagating fronts fully account for the increase in viscosity with applied stress reported by the rheometer and are consistent with the existence of a stable jammed region in contact with one boundary of the system that generates a propagating network of percolated frictional contacts spanning the gap between the rheometer plates and producing strong localized dilatant pressure.

The structural role of bacterial eDNA in the formation of biofilm streamers.

Across diverse habitats, bacteria are mainly found as biofilms, surface-attached communities embedded in a self-secreted matrix of extracellular polymeric substances (EPS), which enhance bacterial recalcitrance to antimicrobial treatment and mechanical stresses. In the presence of flow and geometric constraints such as corners or constrictions, biofilms can take the form of long, suspended filaments (streamers), which bear important consequences in industrial and clinical settings by causing clogging and fouling. The formation of streamers is thought to be driven by the viscoelastic nature of the biofilm matrix. Yet, little is known about the structural composition of streamers and how it affects their mechanical properties. Here, using a microfluidic platform that allows growing and precisely examining biofilm streamers, we show that extracellular DNA (eDNA) constitutes the backbone and is essential for the mechanical stability of Pseudomonas aeruginosa streamers. This finding is supported by the observations that DNA-degrading enzymes prevent the formation of streamers and clear already formed ones and that the antibiotic ciprofloxacin promotes their formation by increasing the release of eDNA. Furthermore, using mutants for the production of the exopolysaccharide Pel, an important component of P. aeruginosa EPS, we reveal an concurring role of Pel in tuning the mechanical properties of the streamers. Taken together, these results highlight the importance of eDNA and of its interplay with Pel in determining the mechanical properties of P. aeruginosa streamers and suggest that targeting the composition of streamers can be an effective approach to control the formation of these biofilm structures.

Flow in temporally and spatially varying porous media: a model for transport of interstitial fluid in the brain.

Flow in a porous medium can be driven by the deformations of the boundaries of the porous domain. Such boundary deformations locally change the volume fraction accessible by the fluid, creating non-uniform porosity and permeability throughout the medium. In this work, we construct a deformation-driven porous medium transport model with spatially and temporally varying porosity and permeability that are dependent on the boundary deformations imposed on the medium. We use this model to study the transport of interstitial fluid along the basement membranes in the arterial walls of the brain. The basement membrane is modeled as a deforming annular porous channel with the compressible pore space filled with an incompressible, Newtonian fluid. The role of a forward propagating peristaltic heart pulse wave and a reverse smooth muscle contraction wave on the flow within the basement membranes is investigated. Our results identify combinations of wave amplitudes that can induce either forward or reverse transport along these transport pathways in the brain. The magnitude and direction of fluid transport predicted by our model can help in understanding the clearance of fluids and solutes along the Intramural Periarterial Drainage route and the pathology of cerebral amyloid angiopathy.

Impaired TRPV4-eNOS signaling in trabecular meshwork elevates intraocular pressure in glaucoma.

Primary Open Angle Glaucoma (POAG) is the most common form of glaucoma that leads to irreversible vision loss. Dysfunction of trabecular meshwork (TM) tissue, a major regulator of aqueous humor (AH) outflow resistance, is associated with intraocular pressure (IOP) elevation in POAG. However, the underlying pathological mechanisms of TM dysfunction in POAG remain elusive. In this regard, transient receptor potential vanilloid 4 (TRPV4) cation channels are known to be important Ca2+ entry pathways in multiple cell types. Here, we provide direct evidence supporting Ca2+ entry through TRPV4 channels in human TM cells and show that TRPV4 channels in TM cells can be activated by increased fluid flow/shear stress. TM-specific TRPV4 channel knockout in mice elevated IOP, supporting a crucial role for TRPV4 channels in IOP regulation. Pharmacological activation of TRPV4 channels in mouse eyes also improved AH outflow facility and lowered IOP. Importantly, TRPV4 channels activated endothelial nitric oxide synthase (eNOS) in TM cells, and loss of eNOS abrogated TRPV4-induced lowering of IOP. Remarkably, TRPV4-eNOS signaling was significantly more pronounced in TM cells compared to Schlemm's canal cells. Furthermore, glaucomatous human TM cells show impaired activity of TRPV4 channels and disrupted TRPV4-eNOS signaling. Flow/shear stress activation of TRPV4 channels and subsequent NO release were also impaired in glaucomatous primary human TM cells. Together, our studies demonstrate a central role for TRPV4-eNOS signaling in IOP regulation. Our results also provide evidence that impaired TRPV4 channel activity in TM cells contributes to TM dysfunction and elevated IOP in glaucoma.

Unstable Coalescence Mechanism and Influencing Factors of Heterogeneous Oil Droplets.

The use of a surfactant solution during oil and gas field development might improve the recovery rate of oil reservoirs. However, the serious emulsification of the produced liquid will bring challenges to the subsequent treatment process and storage and transportation. It is urgent to understand the coalescence mechanism of crude oil under the action of surfactant solution. This research investigates the coalescence mechanism of numerous oil droplets under liquid flow perturbation. The model was established to study the coalescence process of multiple oil droplets. The effects of the number of oil droplets under homogeneous conditions, the size of oil droplets, and the distance between oil droplets under non-homogeneous conditions on the coalescence process were analyzed. Meanwhile, the change rules of the completion time of oil droplet coalescence were drawn. The results show that the smaller the size of individual oil droplets under non-homogeneous conditions, the longer the coalescence completion time is, and when the size of individual oil droplets reaches the nanometer scale, the time for coalescence of oil droplets is dramatically prolonged. Compared to static circumstances, the time it takes for oil droplets to coalesce is somewhat shorter under gravity. In the fluid flow process, in the laminar flow zone, the coalescence time of oil droplets decreases with the increase of the liquid flow rate. However, in the turbulent flow zone, the coalescence time of oil droplets increases with the increase in the liquid flow rate. The coalescence time is in the range of 600~1000 ms in the flow rate of 0.05~0.2 m/s. In the presence of surfactants, the oil content in the emulsion system increases under the influence of pumping flow. The change in oil content rate with various surfactants is less impacted by flow rate, owing to the stable emulsion structure created by the extracted fluid within the reservoir. The study findings presented in this research provide technical assistance for effective crude oil storage and transportation.

Environmental, Microbiological, and Immunological Features of Bacterial Biofilms Associated with Implanted Medical Devices.

The spread of biofilms on medical implants represents one of the principal triggers of persistent and chronic infections in clinical settings, and it has been the subject of many studies in the past few years, with most of them focused on prosthetic joint infections. We review here recent works on biofilm formation and microbial colonization on a large variety of indwelling devices, ranging from heart valves and pacemakers to urological and breast implants and from biliary stents and endoscopic tubes to contact lenses and neurosurgical implants. We focus on bacterial abundance and distribution across different devices and body sites and on the role of environmental features, such as the presence of fluid flow and properties of the implant surface, as well as on the interplay between bacterial colonization and the response of the human immune system.

Bacteria in Fluid Flow.

Bacteria thrive in environments rich in fluid flow, such as the gastrointestinal tract, bloodstream, aquatic systems, and the urinary tract. Despite the importance of flow, how flow affects bacterial life is underappreciated. In recent years, the combination of approaches from biology, physics, and engineering has led to a deeper understanding of how bacteria interact with flow. Here, we highlight the wide range of bacterial responses to flow, including changes in surface adhesion, motility, surface colonization, quorum sensing, virulence factor production, and gene expression. To emphasize the diversity of flow responses, we focus our review on how flow affects four ecologically distinct bacterial species: Escherichia coli, Staphylococcus aureus, Caulobacter crescentus, and Pseudomonas aeruginosa. Additionally, we present experimental approaches to precisely study bacteria in flow, discuss how only some flow responses are triggered by shear force, and provide perspective on flow-sensitive bacterial signaling.

On being the right shape: Roles for motile cilia and cerebrospinal fluid flow in body and spine morphology.

How developing and growing organisms attain their proper shape is a central problem of developmental biology. In this review, we investigate this question with respect to how the body axis and spine form in their characteristic linear head-to-tail fashion in vertebrates. Recent work in the zebrafish has implicated motile cilia and cerebrospinal fluid flow in axial morphogenesis and spinal straightness. We begin by introducing motile cilia, the fluid flows they generate and their roles in zebrafish development and growth. We then describe how cilia control body and spine shape through sensory cells in the spinal canal, a thread-like extracellular structure called the Reissner fiber, and expression of neuropeptide signals. Last, we discuss zebrafish mutants in which spinal straightness breaks down and three-dimensional curves form. These curves resemble the common but little-understood human disease Idiopathic Scoliosis. Zebrafish research is therefore poised to make progress in our understanding of this condition and, more generally, how body and spine shape is acquired and maintained through development and growth.

Fluid flow dynamics in cellular patterning.

The development of complex forms of multicellular organisms depends on the spatial arrangement of cellular architecture and functions. The interior design of the cell is patterned by spatially biased distributions of molecules and biochemical reactions in the cytoplasm and/or on the plasma membrane. In recent years, a dynamic change in the cytoplasmic fluid flow has emerged as a key physical process of driving long-range transport of molecules to particular destinations within the cell. Here, recent experimental advances in the understanding of the generation of the various types of cytoplasmic flows and contributions to intracellular patterning are reviewed with a particular focus on feedback mechanisms between the mechanical properties of fluid flow and biochemical signaling during animal cell polarization.

Functional maturation of kidney organoid tubules: PIEZO1-mediated Ca2+ signaling.

Kidney organoids cultured on adherent matrices in the presence of superfusate flow generate vascular networks and exhibit more mature podocyte and tubular compartments compared with static controls (Homan KA, Gupta N, Kroll KT, Kolesky DB, Skylar-Scott M, Miyoshi T, Mau D, Valerius MT, Ferrante T, Bonventre JV, Lewis JA, Morizane R. Nat Methods 16: 255-262, 2019; Takasato M, Er PX, Chiu HS, Maier B, Baillie GJ, Ferguson C, Parton RG, Wolvetang EJ, Roost MS, Chuva de Sousa Lopes SM, Little MH. Nature 526: 564-568, 2015.). However, their physiological function has yet to be systematically investigated. Here, we measured mechano-induced changes in intracellular Ca2+ concentration ([Ca2+]i) in tubules isolated from organoids cultured for 21-64 days, microperfused in vitro or affixed to the base of a specimen chamber, and loaded with fura-2 to measure [Ca2+]i. A rapid >2.5-fold increase in [Ca2+]i from a baseline of 195.0 ± 22.1 nM (n = 9; P ≤ 0.001) was observed when microperfused tubules from organoids >40 days in culture were subjected to luminal flow. In contrast, no response was detected in tubules isolated from organoids <30 days in culture. Nonperfused tubules (41 days) subjected to a 10-fold increase in bath flow rate also exhibited a threefold increase in [Ca2+]i from baseline (P < 0.001). Mechanosensitive PIEZO1 channels contribute to the flow-induced [Ca2+]i response in mouse distal tubule (Carrisoza-Gaytan R, Dalghi MG, Apodaca GL, Kleyman TR, Satlin LM. The FASEB J 33: 824.25, 2019.). Immunodetectable apical and basolateral PIEZO1 was identified in tubular structures by 21 days in culture. Basolateral PIEZO1 appeared to be functional as basolateral exposure of nonperfused tubules to the PIEZO1 activator Yoda 1 increased [Ca2+]i (P ≤ 0.001) in segments from organoids cultured for >30 days, with peak [Ca2+]i increasing with advancing days in culture. These results are consistent with a maturational increase in number and/or activity of flow/stretch-sensitive Ca2+ channels, including PIEZO1, in tubules of static organoids in culture.

Prostanoid receptors in hyperfiltration-mediated glomerular injury: Novel agonists and antagonists reveal opposing roles for EP2 and EP4 receptors.

Increased fluid-flow shear stress (FFSS) contributes to hyperfiltration-induced podocyte and glomerular injury resulting in progression of chronic kidney disease (CKD). We reported that increased FFSS in vitro and in vivo upregulates PGE2 receptor EP2 (but not EP4 expression), COX2-PGE2 -EP2 axis, and EP2-linked Akt-GSK3ß-ß-catenin signaling pathway in podocytes. To understand and use the disparities between PGE2 receptors, specific agonists, and antagonists of EP2 and EP4 were used to assess phosphorylation of Akt, GSK3ß and ß-catenin in podocytes using Western blotting, glomerular filtration barrier function using in vitro albumin permeability (Palb ) assay, and mitigation of hyperfiltration-induced injury in unilaterally nephrectomized (UNX) mice at 1 and 6 months. Results show an increase in Palb by PGE2 , EP2 agonist (EP2AGO ) and EP4 antagonist (EP4ANT ), but not by EP2 antagonist (EP2ANT ) or EP4 agonist (EP4AGO ). Pretreatment with EP2ANT blocked the effect of PGE2 or EP2AGO on Palb . Modulation of EP2 and EP4 also induced opposite effects on phosphorylation of Akt and ß-Catenin. Individual agonists or antagonists of EP2 or EP4 did not induce significant improvement in albuminuria in UNX mice. However, treatment with a combination EP2ANT + EP4AGO for 1 or 6 months caused a robust decrease in albuminuria. EP2ANT + EP4AGO combination did not impact adaptive hypertrophy or increased serum creatinine. Observed differences between expression of EP2 and EP4 on the glomerular barrier highlight these receptors as potential targets for intervention. Safe and effective mitigating effect of EP2ANT + EP4AGO presents a novel opportunity to delay the progression of hyperfiltration-associated CKD as seen in transplant donors.

Portable and integrated microfluidic flow control system using off-the-shelf components towards organs-on-chip applications.

Organ-on-a-chip (OoC) devices require the precise control of various media. This is mostly done using several fluid control components, which are much larger than the typical OoC device and connected through fluidic tubing, i.e., the fluidic system is not integrated, which inhibits the system's portability. Here, we explore the limits of fluidic system integration using off-the-shelf fluidic control components. A flow control configuration is proposed that uses a vacuum to generate a fluctuation-free flow and minimizes the number of components used in the system. 3D printing is used to fabricate a custom-designed platform box for mounting the chosen smallest footprint components. It provides flexibility in arranging the various components to create experiment-specific systems. A demonstrator system is realized for lung-on-a-chip experiments. The 3D-printed platform box is 290 mm long, 240 mm wide and 37 mm tall. After integrating all the components, it weighs 4.8 kg. The system comprises of a switch valve, flow and pressure controllers, and a vacuum pump to control the diverse media flows. The system generates liquid flow rates ranging from 1.5 [Formula: see text]Lmin[Formula: see text] to 68 [Formula: see text]Lmin[Formula: see text] in the cell chambers, and a cyclic vacuum of 280 mbar below atmospheric pressure with 0.5 Hz frequency in the side channels to induce mechanical strain on the cells-substrate. The components are modular for easy exchange. The battery operated platform box can be mounted on either upright or inverted microscopes and fits in a standard incubator. Overall, it is shown that a compact integrated and portable fluidic system for OoC experiments can be constructed using off-the-shelf components. For further down-scaling, the fluidic control components, like the pump, switch valves, and flow controllers, require significant miniaturization while having a wide flow rate range with high resolution.

Rheotaxis in Mycoplasma gliding.

This review describes the upstream-directed movement in the small parasitic bacterium Mycoplasma. Many Mycoplasma species exhibit gliding motility, a form of biological motion over surfaces without the aid of general surface appendages such as flagella. The gliding motility is characterized by a constant unidirectional movement without changes in direction or backward motion. Unlike flagellated bacteria, Mycoplasma lacks the general chemotactic signaling system to control their moving direction. Therefore, the physiological role of directionless travel in Mycoplasma gliding remains unclear. Recently, high-precision measurements under an optical microscope have revealed that three species of Mycoplasma exhibited rheotaxis, that is, the direction of gliding motility is lead upstream by the water flow. This intriguing response appears to be optimized for the flow patterns encountered at host surfaces. This review provides a comprehensive overview of the morphology, behavior, and habitat of Mycoplasma gliding, and discusses the possibility that the rheotaxis is ubiquitous among them.

Morphogenesis of Biofilms in Porous Media and Control on Hydrodynamics.

The functioning of natural and engineered porous media, like soils and filters, depends in many cases on the interplay between biochemical processes and hydrodynamics. In such complex environments, microorganisms often form surface-attached communities known as biofilms. Biofilms can take the shape of clusters, which alter the distribution of fluid flow velocities within the porous medium, subsequently influencing biofilm growth. Despite numerous experimental and numerical efforts, the control of the biofilm clustering process and the resulting heterogeneity in biofilm permeability is not well understood, limiting our predictive abilities for biofilm-porous medium systems. Here, we use a quasi-2D experimental model of a porous medium to characterize biofilm growth dynamics for different pore sizes and flow rates. We present a method to obtain the time-resolved biofilm permeability field from experimental images and use the obtained permeability field to compute the flow field through a numerical model. We observe a biofilm cluster size distribution characterized by a spectrum slope evolving in time between -2 and -1, a fundamental measure that can be used to create spatio-temporal distributions of biofilm clusters for upscaled models. We find a previously undescribed biofilm permeability distribution, which can be used to stochastically generate permeability fields within biofilms. An increase in velocity variance for a decrease in physical heterogeneity shows that the bioclogged porous medium behaves differently than expected from studies on heterogeneity in abiotic porous media.

Zebrafish: an important model for understanding scoliosis.

Scoliosis is a common spinal deformity that considerably affects the physical and psychological health of patients. Studies have shown that genetic factors play an important role in scoliosis. However, its etiopathogenesis remain unclear, partially because of the genetic heterogeneity of scoliosis and the lack of appropriate model systems. Recently, the development of efficient gene editing methods and high-throughput sequencing technology has made it possible to explore the underlying pathological mechanisms of scoliosis. Owing to their susceptibility for developing scoliosis and high genetic homology with human, zebrafish are increasingly being used as a model for scoliosis in developmental biology, genetics, and clinical medicine. Here, we summarize the recent advances in scoliosis research on zebrafish and discuss the prospects of using zebrafish as a scoliosis model.

Closing the osteon: Do osteocytes sense strain rate rather than fluid flow?

Osteons are cylindrical structures of bone created by matrix resorbing osteoclasts, followed by osteoblasts that deposit new bone. Osteons align with the principal loading direction and it is thought that the osteoclasts are directed by osteocytes, the mechanosensitive cells that reside inside the bone matrix. These osteocytes are presumably controlled by interstitial fluid flow, induced by the physiological loading of bones. Here I consider the stimulation of osteocytes while the osteon is closed by osteoblasts. In a conceptual finite element model, bone is considered a poro-elastic material and subjected to locomotion-induced loading conditions. It appears that the magnitude of flow is constant along the closing cone, while shear strain rate in the bone matrix diminishes linearly with the deposition of bone. This suggests that shear strain rate, rather than fluid flow, is the physical cue that controls osteocytes and bone deposition in newly formed osteons.

The mechanoresponse of bone is closely related to the osteocyte lacunocanalicular network architecture.

Organisms rely on mechanosensing mechanisms to adapt to changes in their mechanical environment. Fluid-filled network structures not only ensure efficient transport but can also be employed for mechanosensation. The lacunocanalicular network (LCN) is a fluid-filled network structure, which pervades our bones and accommodates a cell network of osteocytes. For the mechanism of mechanosensation, it was hypothesized that load-induced fluid flow results in forces that can be sensed by the cells. We use a controlled in vivo loading experiment on murine tibiae to test this hypothesis, whereby the mechanoresponse was quantified experimentally by in vivo micro-computed tomography (µCT) in terms of formed and resorbed bone volume. By imaging the LCN using confocal microscopy in bone volumes covering the entire cross-section of mouse tibiae and by calculating the fluid flow in the three-dimensional (3D) network, we could perform a direct comparison between predictions based on fluid flow velocity and the experimentally measured mechanoresponse. While local strain distributions estimated by finite-element analysis incorrectly predicts preferred bone formation on the periosteal surface, we demonstrate that additional consideration of the LCN architecture not only corrects this erroneous bias in the prediction but also explains observed differences in the mechanosensitivity between the three investigated mice. We also identified the presence of vascular channels as an important mechanism to locally reduce fluid flow. Flow velocities increased for a convergent network structure where all of the flow is channeled into fewer canaliculi. We conclude that, besides mechanical loading, LCN architecture should be considered as a key determinant of bone adaptation.