Low Shear Stress Levels Research Articles

A dynamic flow fetal membrane organ-on-a-chip system for modeling the effects of amniotic fluid motion.

Fetal membrane (amniochorion), the innermost lining of the intrauterine cavity, surround the fetus and enclose amniotic fluid. Unlike unidirectional blood flow, amniotic fluid subtly rocks back and forth, and thus, the innermost amnion epithelial cells are continuously exposed to low levels of shear stress from fluid undulation. Here, we tested the impact of fluid motion on amnion epithelial cells (AECs) as a bearer of force impact and their potential vulnerability to cytopathologic changes that can destabilize fetal membrane functions. A previously developed amnion membrane (AM) organ-on-chip (OOC) was utilized but with dynamic flow to culture human fetal amnion membrane cells. The applied flow was modulated to perfuse culture media back and forth for 48h to mimic fluid motion. A static culture condition was used as a negative control, and oxidative stress (OS) condition was used as a positive control representing pathophysiological changes. The impacts of fluidic motion were evaluated by measuring cell viability, cellular transition, and inflammation. Additionally, scanning electron microscopy (SEM) imaging was performed to observe microvilli formation. The results show that regardless of the applied flow rate, AECs and AMCs maintained their viability, morphology, innate meta-state, and low production of pro-inflammatory cytokines. E-cadherin expression and microvilli formation in the AECs were upregulated in a flow rate-dependent fashion; however, this did not impact cellular morphology or cellular transition or inflammation. OS treatment induced a mesenchymal morphology, significantly higher vimentin to cytokeratin 18 (CK-18) ratio, and pro-inflammatory cytokine production in AECs, whereas AMCs did not respond in any significant manner. Fluid motion and shear stress, if any, did not impact AEC cell function and did not cause inflammation. Thus, when using an amnion membrane OOC model, the inclusion of a dynamic flow environment is not necessary to mimic in utero physiologic cellular conditions of an amnion membrane.

A Dynamic Flow Fetal Membrane Organ-on-a-Chip System for Modeling the Effects of Amniotic Fluid Motion.

Fetal membrane(amniochorion), the innermost lining of the intrauterine cavity, surround the fetus and enclose amniotic fluid. Unlike unidirectional blood flow, amniotic fluid subtly rocks back and forth, and thus, the innermost amnion epithelial cells are continuously exposed to low levels of shear stress from fluid undulation. Here, we tested the impact of fluid motion on amnion epithelial cells (AECs) as a bearer of force impact and their potential vulnerability to cytopathologic changes that can destabilize fetal membrane functions. An amnion membrane (AM) organ-on-chip (OOC) was utilized to culture human fetal amnion membrane cells. The applied flow was modulated to perfuse culture media back and forth for 48 hours flow culture to mimic fluid motion. Static culture condition was used as a negative control, and oxidative stress (OS) condition was used as a positive control for pathophysiological changes. The impacts of fluidic motion were evaluated by measuring cell viability, cellular transition, and inflammation. Additionally, scanning electron microscopy (SEM) imaging was performed to observe microvilli formation. The results show that regardless of the applied flow rate, AECs and AMCs maintained their viability, morphology, innate meta-state, and low production of pro-inflammatory cytokines. E-cadherin expression and microvilli formation in the AECs were upregulated in a flow rate-dependent fashion; however, this did not impact cellular morphology or cellular transition or inflammation. OS treatment induced a mesenchymal morphology, significantly higher vimentin to CK-18 ratio, and pro-inflammatory cytokine production in AECs, whereas AMCs did not respond in any significant manner. Fluid motion and shear stress, if any, did not impact AEC cell function and did not cause inflammation. Thus, when using an amnion membrane OOC model, the inclusion of a flow culture environment is not necessary to mimic any in utero physiologic cellular conditions of fetal membrane-derived cells.

Fluid mechanical performance of ureteral stents: The role of side hole and lumen size.

Ureteral stents are indispensable devices in urological practice to maintain and reinstate the drainage of urine in the upper urinary tract. Most ureteral stents feature openings in the stent wall, referred to as side holes (SHs), which are designed to facilitate urine flux in and out of the stent lumen. However, systematic discussions on the role of SH and stent lumen size in regulating flux and shear stress levels are still lacking. In this study, we leveraged both experimental and numerical methods, using microscopic-Particle Image Velocimetry and Computational Fluid Dynamic models, respectively, to explore the influence of varying SH and lumen diameters. Our results showed that by reducing the SH diameter from to the median wall shear stress levels of the SHs near the ureteropelvic junction and ureterovesical junction increased by over , even though the flux magnitudes through these SH decreased by about . All other SHs were associated with low flux and low shear stress levels. Reducing the stent lumen diameter significantly impeded the luminal flow and the flux through SHs. By means of zero-dimensional models and scaling relations, we summarized previous findings on the subject and argued that the design of stent inlet/outlet is key in regulating the flow characteristics described above. Finally, we offered some clinically relevant input in terms of choosing the right stent for the right patient.

Exercise‐Induced Shear Stress Upregulates eNOS Protein in vitro

BackgroundEndothelial cell dysfunction has been shown to be the first step in the pathogenesis of cardiovascular disease. A risk factor in the development of cardiovascular disease is physical inactivity. Endothelial shear stress (ESS) involves mechanoreceptors on the surface of endothelial cells that are capable of sensing different forces, triggering a biochemical response leading to cellular adaptations. Exercise‐induced ESS might act as a protective mechanism in preventing endothelial cell dysfunction. Endothelial nitric oxide synthase (eNOS), a key enzyme involved maintaining vascular homeostasis has been shown to be upregulated in response to higher shear stress levels. Although exercise has been shown to improve endothelial cell function, the role of varying exercise intensities on endothelial cell homeostasis has not been explored. The purpose of this study was to determine the effects of in vitro exercise‐induced ESS during 3 different exercise intensities on eNOS expression.MethodsCommercially available human umbilical vein endothelial cells (HUVEC; Sigma‐Aldrich, St Louis, MO) were cultured until 90‐100% confluence. Exercise‐induced ESS in vivo was obtained from our previous reports. Cultured cells were exposed to pulsatile resting ESS (18 dynes/cm2) for 2 hours, followed by 1 hour at resting ESS, low‐intensity exercise‐induced ESS (35 dynes/cm2), moderate‐intensity exercise‐induced ESS (50 dynes/cm2), or high‐intensity exercise‐induced ESS (75 dynes/cm2) on a closed circuit pump and channeled slide (Ibidi pump system (PumpControl Software 1.5.4) and slides, Ibidi Inc., Fitchburg, WI). A set of cells were exposed to physiologically low shear stress levels (10 dynes/cm2) for 3 hours as a control. Following ESS conditions, total protein was extracted, and western immunoblotting was performed to measure eNOS protein expression with GAPDH used as the normalizing protein. Statistical analysis was performed using graphpad prism 8 software (Graphpad Software.). Significance was considered at p<0.05.ResultsLow and moderate intensity ESS increased eNOS protein expression compared to physiologically low conditions (P<0.05). There was a trend showing high intensity ESS increasing eNOS expression compared to physiologically low conditions (p<0.10). Additionally, moderate intensity ESS showed a significant increase in eNOS compared to resting conditions (P<0.05).ConclusionsOur data shows that exercise‐induced ESS upregulates eNOS expression. Moderate intensity exercise was shown to produce the highest levels of eNOS expression. Our results from previous studies also show that moderate intensity exercise is capable of activating eNOS, which may act as a protective mechanism to prevent atherosclerosis development.

Higher Levels of Shear Stress Downregulate Endothelin‐1 mRNA Expression

BackgroundPhysical inactivity has been shown to be a risk factor in the development of endothelial dysfunction. Endothelin‐1 (EDN‐1), a potent vasoconstrictor contributes to the pathogenesis of cardiovascular disease. Exercise‐induced endothelial shear stress (ESS) is a mechanical stimulus caused by alterations in blood flow patterns that regulates vascular function. Although it has been reported that higher levels of ESS may act as a protective mechanism to prevent vascular dysfunction, the role of pulsatile exercise‐induced ESS with varying exercise intensities has not been explored. Therefore, the purpose of this study was to determine the effects of pulsatile exercise‐induced ESS based on in vivo exercise intensity on EDN‐1 expression.MethodsCommercially available human umbilical vein endothelial cells (HUVEC; Sigma‐Aldrich, St Louis, MO) were cultured until 90–100% confluence. Exercise‐induced ESS in vivo was obtained from our previous reports. Cultured HUVEC cells were exposed to pulsatile resting ESS (18 dynes/cm2) for 2 hours, followed by 1 hour at resting ESS, low‐intensity exercise‐induced ESS (35 dynes/cm2), moderate exercise‐induced ESS, or high‐intensity exercise‐induced ESS (75 dynes/cm2) on a closed circuit pump and channeled slide (Ibidi pump system (PumpControl Software 1.5.4) and slides, Ibidi Inc., Fitchburg, WI). A set of cells were exposed to physiologically low shear stress levels (10 dynes/cm2) for 3 hours as a control. Total RNA was extracted and reverse transcribed followed by measurement of EDN‐1 mRNA expression via qRT‐PCR. qRT‐PCRs were performed in duplicates and changes in gene expression were calculated using the ΔΔ‐CT method with GAPDH used as the normalizing control gene. Statistical analysis was performed using graphpad prism 8 software (Graphpad Software.). Significance was considered at p<0.05.ResultsEDN‐1 mRNA expression was significantly downregulated following low and high intensity exercise‐induced ESS compared to resting conditions (p<0.05). Moderate intensity exercise induced ESS showed a trend downregulation in EDN‐1 mRNA expression compared to resting conditions (p<0.10).ConclusionsOur data suggests that higher levels of pulsatile exercise‐induced ESS are needed to suppress mRNA expression of EDN‐1. Although moderate intensity exercise induced ESS showed only a trend difference in mRNA expression compared to resting conditions, we have previously reported that moderate exercise‐induced ESS was shown to upregulate endothelial nitric oxide gene expression, a key vasodilatory enzyme that may prevent vascular dysfunction.

Quantitative prediction of rolling dynamics of leukocyte-inspired microroller in blood flow

A magnetic microroller, inspired by leukocytes (also called white blood cells, WBCs) in the microcirculatory system, represents a promising candidate for targeted drug delivery. However, the rolling dynamics of an individual microroller in response to controlled changes in shear stress and magnetic fields remains largely unknown. Here, we develop a mesoscopic model of the WBC-inspired microroller to investigate its locomotion behavior inside blood vessels under different shear stresses and magnetic torques. We find that the microroller can roll along with the blood flow or move against the bloodstream depending upon the competition between the applied magnetic torque and fluid shear stress. Our simulations reveal that the microroller can achieve precise navigation under low shear stress levels. We also probe the effect of the blood hematocrit on the dynamic performance of the microroller, which shows that shear-induced collisions between erythrocytes (also called red blood cells) and the microroller can significantly alter the motion of the microroller, especially under high hematocrit levels. In addition, we examine the rolling dynamics of the WBC-inspired microroller in a bifurcating microfluidic channel, demonstrating that the microroller can navigate along the user-defined path. These findings provide unique insights into the rolling dynamics of the individual microroller in physiologically relevant blood flow and offer an objective way for facilitating the design of bioinspired microrollers in targeted and localized therapeutic delivery with high precision and efficiency.

Prediction of Joint Shear Deformation Index of RC Beam–Column Joints

In the analysis of reinforced concrete (RC) buildings, beam–column joints are regarded as rigid nodes. In fact, joint deformation may make a significant difference in the lateral response of RC buildings if joints are not properly designed and detailed. To consider joint flexibility, several types of joint models have been proposed. However, these models require complicated computations, consequently making them challenging to apply in engineering practice. This paper proposed a simple approach for predicting the contribution of the joint deformation to the total deformation of RC interior beam–column joints under critical structural deformations. To develop such a simple and accurate approach, experimental and analytical studies were performed on RC interior beam–column joints. In this study, eight half-scale joint specimens were tested under reversed cyclic loading, and 39 full–scale FE models were constructed, varying the selected key parameters. The experimental and analytical results showed that the “joint shear” is a useful index for the beam–column joints with high shear stress levels of vj>1.7 fc′ but is unsuitable for defining the failure of beam–column joints with medium or low shear stress levels of vj≈1.25–1.7fc′ and vj≈1.0fc′. Based on the results, three equations were developed to predict the joint shear deformation index (SDI) of RC interior beam–column connections corresponding to three different types of failure (i.e., joint failure before beam yielding, joint failure after beam yielding, and beam flexural failure). SDI predictions of the proposed equations correlate well with 50 test results of beam–column joints available from the literature.

Analyzing the shear-induced sensitization of mechanosensitive ion channel Piezo-1 in human aortic endothelial cells.

Mechanosensitive ion channels mediate endothelial responses to blood flow and orchestrate their physiological function in response to hemodynamic forces. In this study, we utilized microfluidic technologies to study the shear-induced sensitization of endothelial Piezo-1 to its selective agonist, Yoda-1. We demonstrated that shear stress-induced sensitization is brief and can be impaired when exposing aortic endothelial cells to low and proatherogenic levels of shear stress. Our results suggest that shear stress-induced sensitization of Piezo-1 to Yoda-1 is independent of cell-cell adhesion and is mediated by the PI3K-AKT signaling pathway. We also found that shear stress increases the membrane density of Piezo-1 channels in endothelial cells. To further confirm our findings, we performed experiments using a carotid artery ligation mouse model and demonstrated that transient changes in blood-flow pattern, resulting from a high-degree ligation of the mouse carotid artery alters the distribution of Piezo-1 channels across the endothelial layer. These results suggest that shear stress influences the function of Piezo-1 channels via changes in membrane density, providing a new model of shear-stress sensitivity for Piezo-1 ion channel.

Abstract 5012: Exercise as a novel method of tumor vascular remodeling

Abstract Chemotherapy efficacy is reliant upon access to tumor cells. One method of increasing chemotherapy response is to enhance delivery of chemotherapy to the tumor by vascular normalization. Tumor vasculature is largely dysfunctional, leading to poor delivery of chemotherapy. Vascular normalization, the remodeling of tumor vessels to increase functionality, has been shown to improve drug delivery and response in patients with glioblastoma, ovarian and colorectal cancers. Current normalization strategies using anti-angiogenic agents have a narrow dose and time therapeutic window. Therefore, it is imperative to identify other methods of inducing tumor vessel normalization to enhance the delivery and efficacy of chemotherapy. Vascular development, and endothelial cell (EC) signaling, is controlled by shear stress. Shear stress is the mechanical force exerted on ECs by blood flow through the vessel lumen. The role of shear stress in tumor vessel development is poorly understood. Tumors have heterogeneous, low levels of vascular shear stress. Heterogeneous, low shear stress causes hyper-permeable vessels that inefficiently deliver blood throughout the tumor. Aerobic exercise is a well-studied method for increasing vascular shear stress. We demonstrated in mouse models of Ewing sarcoma and melanoma that increasing shear stress via moderate exercise caused improved tumor vascular function including reduced hyper-permeability. This correlated with significantly increased chemotherapy delivery and efficacy; doxorubicin was significantly more effective against both tumor models when combined with exercise. The molecular mechanisms of tumor vascular remodeling in response to exercise, particularly the decrease in vessel permeability leading to better drug delivery, are unclear. Vascular permeability is regulated in part via Sphingosine-1-Phosphate Receptors 1 and 2 (S1PR1, S1PR2) on ECs, which have contrasting effects on angiogenesis. S1PR1 signaling increases adherens junctions, decreasing vascular permeability. In contrast, S1PR2 signaling increases vessel permeability. We found that S1PR1 was increased while S1PR2 was decreased on tumor endothelium of exercised mice. We have now identified the novel regulator of tumor endothelial permeability, ERK5, as a key mediator of improved tumor vascular function in response to exercise. Pharmacologic activation of S1PR1 by SEW2871 or activation of ERK5 signaling by p90RSK decreased tumor vascular hyper-permeability and increased doxorubicin efficacy, mimicking the exercise effect. Ongoing work using inducible S1PR1 or ERK5 knockout mice will determine whether this pathway is essential for exercise-induced tumor vascular remodeling and improved chemotherapeutic efficacy. Citation Format: Hannah Savage, Enrica Marmonti, Claudia Bedoya, Miriam Garcia, Keri Schadler. Exercise as a novel method of tumor vascular remodeling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5012.

A Microfluidic-Based Investigation of Bacterial Attachment in Ureteral Stents.

Obstructions of the ureter lumen can originate from intrinsic or extrinsic factors, such as kidney stones, tumours, or strictures. These can affect the physiological flow of urine from the kidneys to the bladder, potentially causing infection, pain, and kidney failure. To overcome these complications, ureteral stents are often deployed clinically in order to temporarily re-establish urinary flow. Despite their clinical benefits, stents are prone to encrustation and biofilm formation that lead to reduced quality of life for patients; however, the mechanisms underlying the formation of crystalline biofilms in stents are not yet fully understood. In this study, we developed microfluidic-based devices replicating the urodynamic field within different configurations of an occluded and stented ureter. We employed computational fluid dynamic simulations to characterise the flow dynamic field within these models and investigated bacterial attachment (Pseudomonas fluorescens) by means of crystal violet staining and fluorescence microscopy. We identified the presence of hydrodynamic cavities in the vicinity of a ureteric occlusion, which were characterised by low levels of wall shear stress (WSS < 40 mPa), and observed that initiation of bacterial attachment occurred in these specific regions of the stented ureter. Notably, the bacterial coverage area was directly proportional to the number of cavities present in the model. Fluorescence microscopy confirmed that the number density of bacteria was greater within cavities (3 bacteria·mm−2) when compared to side-holes of the stent (1 bacterium·mm−2) or its luminal surface (0.12 bacteria·mm−2). These findings informed the design of a novel technological solution against bacterial attachment, which reduces the extent of cavity flow and increases wall shear stress over the stent’s surface.

Direct-Write Bioprinting Approach to Construct Multilayer Cellular Tissues.

As a cellular-assembly technique, bioprinting has been extensively used in tissue engineering and regenerative medicine to construct hydrogel-based three-dimensional (3D) tissue-like models with prescribed geometry. Here, we introduced a unique direct-write bioprinting strategy to fabricate a bilayer flat tissue in a hydrogel-free approach. A printed retina pigmented epithelium layer (RPE) was applied as living biopaper for positioning a fibroblast layer without using any hydrogel in bioink. We adjusted the number of cells in the inkjet droplets in order to obtain a uniform printed cell layer and demonstrated the formation of a bilayer construct through confocal imaging. Since our printing system introduced low levels of shear stress to the cells, it did not have a negative effect on cell survival, although cell viability was generally lower than that of control group over 1 week post-printing. In conclusion, our novel direct-write bioprinting approach to spatiotemporally position different cellular layers may represent an efficient tool to develop living constructs especially for regeneration of complex flat tissues.

Reducing deposition of encrustation in ureteric stents by changing the stent architecture: A microfluidic-based investigation.

Ureteric stents are clinically deployed to retain ureteral patency in the presence of an obstruction of the ureter lumen. Despite the fact that multiple stent designs have been researched in recent years, encrustation and biofilm-associated infections remain significant complications of ureteral stenting, potentially leading to the functional failure of the stent. It has been suggested that “inactive” side-holes of stents may act as anchoring sites for encrusting crystals, as they are associated with low wall shear stress (WSS) levels. Obstruction of side-holes due to encrustation is particularly detrimental to the function of the stent, since holes provide a path for urine to by-pass the occlusion. Therefore, there is an unmet need to develop novel stents to reduce deposition of encrusting particles at side-holes. In this study, we employed a stent-on-chip microfluidic model of the stented and occluded ureter to investigate the effect of stent architecture on WSS distribution and encrustation over its surface. Variations in the stent geometry encompassed (i) the wall thickness and (ii) the shape of side-holes. Stent thickness was varied in the range 0.3-0.7 mm, while streamlined side-holes of triangular shape were evaluated (with a vertex angle in the range 45°-120°). Reducing the thickness of the stent increased WSS and thus reduced the encrustation rate at side-holes. A further improvement in performance was achieved by using side-holes with a triangular shape; notably, a 45° vertex angle showed superior performance compared to other angles investigated, resulting in a significant increase in WSS within “inactive” side-holes. In conclusion, combining the optimal stent thickness (0.3 mm) and hole vertex angle (45°) resulted in a ∼90% reduction in encrustation rate within side-holes, compared to a standard design. If translated to a full-scale ureteric stent, this optimised architecture has the potential for significantly increasing the stent lifetime while reducing clinical complications.

Endothelial cell dynamics in vascular remodelling.

In this ESCHM 2016 conference talk report, we summarise two recently published original articles Franco et al. PLoS Biology 2015 and Franco et al. eLIFE 2016. The vascular network undergoes extensive vessel remodelling to become fully functional. Is it well established that blood flow is a main driver for vascular remodelling. It has also been proposed that vessel pruning is a central process within physiological vessel remodelling. However, despite its central function, the cellular and molecular mechanisms regulating vessel regression, and their interaction with blood flow patterns, remain largely unexplained. We investigated the cellular process governing developmental vascular remodelling in mouse and zebrafish. We established that polarised reorganization of endothelial cells is at the core of vessel regression, representing vessel anastomosis in reverse. Moreover, we established for the first time an axial polarity map for all endothelial cells together with an in silico method for the computation of the haemodynamic forces in the murine retinal vasculature. Using network-level analysis and microfluidics, we showed that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/11 renders endothelial cells more sensitive to shear, resulting in axial polarisation at lower shear stress levels. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus.

Assessment of the hemodynamic characteristics of Absorb BVS in a porcine coronary artery model

Local hemodynamic changes are one of the main factors that determine the vessel wall biological response after stent/scaffold implantation. Computational fluid dynamic studies provide an opportunity to investigate the rheological effects of implanted stent/scaffold. The aim of this study was to assess the local hemodynamic microenvironment in scaffolded segments in porcine coronary models. In six epicardial coronary arteries of healthy mini-pigs, six Absorb bioresorbable vascular scaffolds (Absorb BVS) were implanted. Optical coherence tomography(OCT) was performed after scaffold implantation and the images were fused with the angiographic data to reconstruct the three-dimensional coronary artery anatomy. Blood flow simulations were performed, and endothelial shear stress(ESS) distribution was estimated for each scaffolded segment. In a linear mixed-effect model, the contributing factors for low (<1.0Pa) ESS levels were assessed. At 30-day post-implantation, histopathological assessment was performed at 2 scaffolds. In scaffolded segments, the median ESS was 0.57 (IQR: 0.29-0.99) Pa. In linear mixed-effect analysis, cross-section area was associated with low shear stress levels. In scaffolded segments, the percentage of the recirculation zone per scaffolded luminal surface was 3.26±2.07%. At 30-day histopathological assessment of implanted vessel segments revealed minimal injury score, minimal neointimal inflammation and minimal adventitial inflammation scores with moderate endothelial coverage. Fibrin accumulation was seen at 95.69±2.47% of the struts. The thick rectangular strut design of the Absorb BVS incited flow disruptions with low shear stress inducing fibrin accumulation. CFD assessment can be used to guide improvements in the scaffold design for a more "hemo-compatible" geometry.

EPAC1 promotes adaptive responses in human arterial endothelial cells subjected to low levels of laminar fluid shear stress: Implications in flow-related endothelial dysfunction

Blood flow-associated fluid shear stress (FSS) dynamically regulates the endothelium's ability to control arterial structure and function. While arterial endothelial cells (AEC) subjected to high levels of laminar FSS express a phenotype resistant to vascular insults, those exposed to low levels of laminar FSS, or to the FSS associated with oscillatory blood flow, are less resilient. Despite numerous reports highlighting how the cAMP-signaling system controls proliferation, migration and permeability of human AECs (HAECs), its role in coordinating HAEC responses to FSS has received scant attention. Herein we show that the cAMP effector EPAC1 is required for HAECs to align and elongate in the direction of flow, and for the induction of several anti-atherogenic and anti-thrombotic genes associated with these events. Of potential therapeutic importance, EPAC1 is shown to play a dominant role the in response of HAECs to low levels of laminar FSS, such as would be found within atherosclerosis-prone areas of the vasculature. Moreover, we show that EPAC1 promotes these HAEC responses to flow by regulating Vascular Endothelial Growth Factor Receptor-2 and Akt activation, within a VE-cadherin (VECAD)/PECAM1-based mechanosensor. We submit that these findings are consistent with the novel proposition that promoting EPAC1-signaling represents a novel means through which to promote expression of an adaptive phenotype in HAECs exposed to non-adaptive FSS-encoded signals as a consequence of vascular disease.

Effects of rhythmic exercise performed to music on the rheological properties of blood in women over 60 years of age

The aim of this study was to analyze the effects of motor rehabilitation, in the form of rhythmic exercise to music, on the rheological characteristics of blood in older women. The study included 30 women (65-80 years of age), and the control group was comprised of 10 women of corresponding age. Women from the experimental group were subjected to a five-month rehabilitation program, in the form of rhythmic exercise performed to music (three 30-minute sessions per week); women from the control group were not involved in any regular physical activity. Blood samples from all the women were examined for hematological, rheological, and biochemical parameters prior to the study and five months thereafter. The rehabilitation program was reflected by a significant improvement of erythrocyte count and hematocrit. Furthermore, an improvement of erythrocyte deformability was observed by lower shear stress levels, while no significant changes were noted by the higher shear stress values. The rehabilitation resulted in a marked decrease of the aggregation amplitude while no significant changes were observed in aggregation index and total aggregation half-time. Additionally, the training regimen was reflected by a significant increase in the plasma viscosity, while no significant changes in fibrinogen levels were noted.

Sediment texture, erodibility, and composition in the Northern Gulf of Mexico and their potential impacts on hypoxia formation

A region of hypoxic waters has formed annually over the past several decades in the northern Gulf of Mexico. This has motivated the studies of mechanisms controlling the development of hypoxia. Both field and laboratory approaches were used to examine sediment texture, erodibility, and composition. Sediment texture analyses show that grain size relates to the proximity to the Mississippi and Atchafalaya river deltas and to the remnants of shifts in the Mississippi and Atchafalaya deltaic lobes. Temporal variability in erodibility relates to seasonal weather patterns, with more energetic wave conditions in winter and spring setting up an active bottom layer that increases erodibility, compared to quiescent summers that allow for seabed consolidation. The amount of eroded material is fairly low until shear stress levels in the bottom boundary layer exceed 0.4 Pa. An organically enriched fluff layer was found at the sediment–water interface, which is highly erodible under low shear stress levels. Eroded volatile suspended solids (a proxy for organic material) vs. increasing levels of shear stress revealed a distinct pattern at all sample areas; higher concentrations of organic material were eroded at the lowest (0.01 Pa) and highest (0.6 Pa) applied shear stresses, and there was a higher ratio of the volatile to total suspended solids at 0.01 Pa. Based on erodibility experiments and modeling data analysis, the low shear stress levels during the quiescent periods in summer were sometimes high enough to resuspend this fluff layer, but not underlying sediment, thereby potentially facilitating the development of bottom water hypoxia.

Rheology evolution of sludge through high-solid anaerobic digestion

The main purpose of this study was to investigate the rheology evolution of sludge through high-solid anaerobic digestion (AD) and its dependency on sludge retention time (SRT) and temperature of AD reactor. The operation performance of high-solid AD reactors were also studied. The results showed that sludge became much more flowable after high-solid AD. It was found that the sludge from reactors with long SRT exhibited low levels of shear stress, viscosity, yield stress, consistency index, and high value of flow behaviour index. While the flowability of sludge from thermophilic AD reactors were better than that of sludge from mesophilic AD reactors though the solid content of the formers were higher than that of the latters, which could be attributed to the fact that the formers had more amount of free and interstitial moisture. It might be feasible to use sludge rheology as an AD process controlling parameter.

Invited Commentary

Moazami and colleagues [1] provide interesting insight into the evolution of mechanical circulatory support in their analysis of the DuraHeart Trial. The DuraHeart pump (Terumo Heart Inc, Ann Arbor, MI) was an engineering marvel, presenting the first fully magnetically levitated left ventricular assist device (LVAD). A frictionless propulsion system, in which the impeller never makes contact with the blood chamber housing, provided low levels of shear stress and minimal hemolysis. The absence of pump thrombosis during the trial provided evidence of success of this elegant engineering design.

Directional Mechanosensing of Amoeboid Cells

The importance of mechanotactic directional motility has proven to be central in a series of recent experiments involving eukaryotic cells. Hydrodynamic shear stress is one biophysical cue in the extracellular matrix that has been shown to generate compelling mechanotactic behaviors. A microfluidic setup has been designed to generate creeping flows with controllable low-magnitude shear stress and with the possibility to swiftly reverse flow direction within one second. This setup allows us to directly visualize and track the transient responses of multiply seeded cells. Using vegetative Dictyostelium discoideum amoebae, we show that crawling cells have enhanced directional mechanosensitivity with environmental conditions close to those encountered in vivo, in terms of shear stress levels, extracellular calcium concentrations and substrate stiffness. Low shear stress levels in the range of 0.2 Pa are able to trigger a cellular response and hence can be used to effectively drive cells to follow predetermined sequences of steps including straightforward motion, immobilization and reversal. In addition, a wide range of extracellular calcium concentrations have been investigated in our study. We found that soluble calcium in the extracellular environment plays an important role in mechanotactic cell guiding and control. The existence of an optimal value for the calcium concentration for both the average cell speed and the directionality can be clearly observed.