The role of skin in the human body is indispensable, serving as a barrier, moderating homeostatic balance, and representing a pronounced endpoint for cosmetics and pharmaceuticals. Despite the ...extensive achievements of in vitro skin models, they do not recapitulate the complexity of human skin; thus, there remains a dependence on animal models during preclinical drug trials, resulting in expensive drug development with high failure rates. By imparting a fine control over the microenvironment and inducing relevant mechanical cues, skin‐on‐a‐chip (SoC) models have circumvented the limitations of conventional cell studies. Enhanced barrier properties, vascularization, and improved phenotypic differentiation have been achieved by SoC models; however, the successful inclusion of appendages such as hair follicles and sweat glands and pigmentation relevance have yet to be realized. The present Review collates the progress of SoC platforms with a focus on their fabrication and the incorporation of mechanical cues, sensors, and blood vessels.
Skin‐on‐a‐chip (SoC) platforms leverage microfluidic technologies to offer fine control over the cellular microenvironment while closely mimicking the structural and functional properties of the human skin. This Review systematically collates and discusses recent progress on SoC development, highlighting the applications of such platforms for studying the response of skin under various stimuli, modeling skin diseases, and drug development.
Molecular Sensors of Blood Flow in Endothelial Cells Baratchi, Sara; Khoshmanesh, Khashayar; Woodman, Owen L. ...
Trends in molecular medicine,
September 2017, 2017-09-00, 20170901, Letnik:
23, Številka:
9
Journal Article
Recenzirano
Mechanical stress from blood flow has a significant effect on endothelial physiology, with a key role in initiating vasoregulatory signals. Disturbances in blood flow, such as in regions of ...disease-associated stenosis, arterial branch points, and sharp turns, can induce proatherogenic phenotypes in endothelial cells. The disruption of vascular homeostasis as a result of endothelial dysfunction may contribute to early and late stages of atherosclerosis, the underlying cause of coronary artery disease. In-depth knowledge of the mechanobiology of endothelial cells is essential to identifying mechanosensory complexes involved in the pathogenesis of atherosclerosis. In this review, we describe different blood flow patterns and summarize current knowledge on mechanosensory molecules regulating endothelial vasoregulatory functions, with clinical implications. Such information may help in the search for novel therapeutic approaches.
Molecular sensors of blood flow enable the translation of mechanical stimuli associated with blood flow into molecular responses that in turn regulate the tension in blood vessels. Identifying such molecules and understanding their function may provide a starting point for the treatment of different cardiovascular pathologies.
Atherosclerosis is closely associated with remodeling of the extracellular matrix via the accumulation of fibronectin in the laminin-collagen basal membrane. Inflammation associated with atherosclerosis is regulated, at least in part, via the interaction of α5 integrins with fibronectin.
Piezo1 is a mechanosensitive ion channel that is proposed to gate directly in response to shear stress. This channel is required for flow-induced ATP release and activation of downstream signaling pathways in endothelial cells and red blood cells.
Shear stress controls exocytosis and interaction of mechanoreceptors, such as transient receptor potential (TRP)V4, cadherins, and integrins, on the cell membrane. These relocations and interactions have important roles in maintaining the physiological functions of blood flow on exposed cells.
The flow-sensing pathway platelet endothelial cell adhesion molecule-1 (PECAM-1)/VE-cadherin/vascular endothelial growth factor receptors (VEGRs), which controls the endothelial alignment to the direction of flow, can regulate atherogenesis and could be targeted to prevent and/or alter the progression of atherosclerosis.
Liquid metal enabled pump Tang, Shi-Yang; Khoshmanesh, Khashayar; Sivan, Vijay ...
Proceedings of the National Academy of Sciences - PNAS,
03/2014, Letnik:
111, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Small-scale pumps will be the heartbeat of many future micro/nanoscale platforms. However, the integration of small-scale pumps is presently hampered by limited flow rate with respect to the input ...power, and their rather complicated fabrication processes. These issues arise as many conventional pumping effects require intricate moving elements. Here, we demonstrate a system that we call the liquid metal enabled pump, for driving a range of liquids without mechanical moving parts, upon the application of modest electric field. This pump incorporates a droplet of liquid metal, which induces liquid flow at high flow rates, yet with exceptionally low power consumption by electrowetting/deelectrowetting at the metal surface. We present theory explaining this pumping mechanism and show that the operation is fundamentally different from other existing pumps. The presented liquid metal enabled pump is both efficient and simple, and thus has the potential to fundamentally advance the field of microfluidics.
Components with self-propelling abilities are important building blocks of small autonomous systems and the characteristics of liquid metals are capable of fulfilling self-propulsion criteria. To ...date, there has been no exploration regarding the effect of electrolyte ionic content surrounding a liquid metal for symmetry breaking that generates motion. Here we show the controlled actuation of liquid metal droplets using only the ionic properties of the aqueous electrolyte. We demonstrate that pH or ionic concentration gradients across a liquid metal droplet induce both deformation and surface Marangoni flow. We show that the Lippmann dominated deformation results in maximum velocity for the self-propulsion of liquid metal droplets and illustrate several key applications, which take advantage of such electrolyte-induced motion. With this finding, it is possible to conceive the propulsion of small entities that are constructed and controlled entirely with fluids, progressing towards more advanced soft systems.
Localized Ca
influx via TRPV4 on the surface of endothelial cells greatly influences endothelial adaptation to blood flow, but how mechanical stress from blood flow controls TRPV4 integration into ...this physiological function is not fully understood. Here, we studied the spatial organization of TRPV4 and its relationship to the adherens junction component β-catenin using single- and dual-color direct stochastic optical reconstruction microscopy (dSTORM). In non-stimulated endothelial cells, TRPV4 is clustered in small protein islands, as is β-catenin. Using dual-color imaging, we found that TRPV4 and β-catenin reside in similar islands and can be found at both the basolateral and basal membranes. Following shear stress stimulation, TRPV4 molecules formed smaller clusters, with the majority residing outside of clusters. Further shear stress stimulation changed the molecular distribution of TRPV4 molecules, limiting them to the basal membrane. This redistribution and the smaller clusters resulted in the segregation of TRPV4 from β-catenin. Furthermore, TRPV4 trafficking was controlled by focal adhesion kinase and activation of the α5ß1 integrin. These highly differentiated spatial redistributions suggest that mechanotransduction of blood flow is controlled via a more complex hierarchy than previously thought.
Raman microscopy systems are becoming increasingly widespread and accessible for characterising chemical species. Microfluidic systems are also progressively finding their way into real world ...applications. Therefore, it is anticipated that the integration of Raman systems with microfluidics will become increasingly attractive and practical. This review aims to provide an overview of Raman microscopy-microfluidics integrated systems for researchers who are actively interested in utilising these tools. The fundamental principles and application strengths of Raman microscopy are discussed in the context of microfluidics. Various configurations of microfluidics that incorporate Raman microscopy methods are presented, with applications highlighted. Data analysis methods are discussed, with a focus on assisting the interpretation of Raman-microfluidics data from complex samples. Finally, possible future directions of Raman-microfluidic systems are presented.
A new platform described as the liquid metal/metal oxide (LM/MO) framework is introduced. The constituent spherical structures of these frameworks are made of micro‐ to nanosized liquid metal spheres ...and nanosized metal oxides, combining the advantages of both materials. It is shown that the diameters of the spheres and the stoichiometry of the structures can be actively controlled. Additionally, the liquid suspension of these spheres demonstrates tuneable plasmon resonances. These spherical structures are assembled to form LM/MO frameworks which are capable of demonstrating high sensitivity towards low concentrations of heavy metal ions, and enhanced solar light driven photocalalytic activities. These demonstrations imply that the LM/MO frameworks are a suitable candidate for the development of future high performance electronic and optical devices.
A new platform described as the liquid metal/metal oxide (LM/MO) framework is introduced. The constituent spherical structures of these frameworks are made of micro‐ to nanosized liquid metal spheres and nanosized metal oxides. These LM/MO frameworks demonstrate high sensitivity towards low concentrations of heavy metal ions and enhanced solar light driven photocalalytic activities.
Chaotic advection plays an important role in microplatforms for a variety of applications. Currently used mechanisms for inducing chaotic advection in small scale, however, are limited by their ...complicated fabrication processes and relatively high power consumption. Here, a soft actuator is reported which utilizes a droplet of Galinstan liquid metal to induce harmonic Marangoni flow at the surface of liquid metal when activated by a sinusoidal signal. This liquid metal actuator has no rigid parts and employs continuous electrowetting effect to induce chaotic advection with exceptionally low power consumption. The theory behind the operation of this actuator is developed and validated via a series of experiments. The presented actuator can be readily integrated into other microfluidic components for a wide range of applications.
A soft actuator is developed which utilizes a droplet of Galinstan liquid metal to induce harmonic Marangoni flow at the surface of liquid metal when activated by a sinusoidal signal. This liquid metal actuator has no rigid parts and can be readily integrated into other microfluidic components for a wide range of applications.
Microfluidic based blood plasma extraction is a fundamental necessity that will facilitate many future lab-on-a-chip based point-of-care diagnostic systems. However, current approaches for providing ...this analyte are hampered by the requirement to provide external pumping or dilution of blood, which result in low effective yield, lower concentration of target constituents, and complicated functionality. This paper presents a capillary-driven, dielectrophoresis-enabled microfluidic system capable of separating and extracting cell-free plasma from small amounts of whole human blood. This process takes place directly on-chip, and without the requirement of dilution, thus eliminating the prerequisite of pre-processed blood samples and external liquid handling systems. The microfluidic chip takes advantage of a capillary pump for driving whole blood through the main channel and a cross flow filtration system for extracting plasma from whole blood. This filter is actively unblocked through negative dielectrophoresis forces, dramatically enhancing the volume of extracted plasma. Experiments using whole human blood yield volumes of around 180 nl of cell-free, undiluted plasma. We believe that implementation of various integrated biosensing techniques into this plasma extraction system could enable multiplexed detection of various biomarkers.
Photobiomodulation (PBM) refers to the use of light to modulate cellular processes, and has demonstrated utility in improving wound healing outcomes, and reducing pain and inflammation. Despite the ...potential benefits of PBM, the precise molecular mechanisms through which it influences cell behavior are not yet well understood. Inconsistent reporting of key light parameters has created uncertainty around optimal exposure profiles. In addition, very low intensities of light, < 0.1 J/cm
, have not been thoroughly examined for their use in PBM. Here, we present a custom-made compact, and modular LED-based exposure system for studying the effects of very low-intensity visible light (cell proliferation, migration, ROS production, and mitochondrial membrane potential) of three different wavelengths in a parallel manner. The device allows for six repeats of three different exposure conditions plus a non-irradiated control on a single 24-well plate. The immortalised human keratinocyte cell line, HaCaT, was selected as a major cellular component of the skin epidermal barrier. Furthermore, an in vitro wound model was developed by allowing the HaCaT to form a confluent monolayer, then scratching the cells with a pipette tip to form a wound. Cells were exposed to yellow (585 nm, 0.09 mW, ~ 3.7 mJ/cm
), orange (610 nm, 0.8 mW, ~ 31 mJ/cm
), and red (660 nm, 0.8 mW, ~ 31 mJ/cm
) light for 10 min. 48 h post-irradiation, immunohistochemistry was performed to evaluate cell viability, proliferation, ROS production, and mitochondrial membrane potential. The results demonstrate increased proliferation and decreased scratch area for all exposure conditions, however only red light increased the mitochondrial activity. Oxidative stress levels did not increase for any of the exposures. The present exposure system provides opportunities to better understand the complex cellular mechanisms driven by the irradiation of skin cells with visible light.
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