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.
Brain , Extracellular Fluid , Extracellular Fluid/metabolism , Extracellular Fluid/physiology , Porosity , Humans , Brain/metabolism , Brain/blood supply , Brain/physiology , Basement Membrane/metabolism , Basement Membrane/physiology , Mathematical Concepts , Biological Transport/physiology , Models, Biological , Computer Simulation , Models, Neurological , Animals , Permeability
Microparticles trapped on the surface of a sessile droplet interact via electrostatic and capillary forces. The assembly of colloids at a fluid-fluid interface is governed by particle size, surface chemistry, and contact line roughness. We created nonspherical droplets using surface energy patterning and delivered microparticles to the liquid-air interface with electrospray atomization. Using a water droplet as the target, the particle assembly was observed over time. We found that the underlying surface energy pattern significantly influenced the colloidal assembly and drove particles toward the center of the droplet. The particles were arranged into a single, non-close-packed cluster with local hexagonal ordering but left a clear region with very few particles near the contact line. This depletion region is attributed to long-range electrostatic repulsion from the photoresist used to create the surface energy pattern, which retained electric charge from the electrospray. To understand the effect of electrostatic interactions, we explored target droplets with dissimilar dielectric properties. Using patterned substrates and electrospray for particle deposition, we can harness the assembly of colloids at a fluid interface to build repeatable monolayer patterns.
We present a microfluidic technique that generates asymmetric giant unilamellar vesicles (GUVs) in the size range of 2-14 µm. In our method, we (i) create water-in-oil emulsions as the precursors to build synthetic vesicles, (ii) deflect the emulsions across two oil streams containing different phospholipids at high throughput to establish an asymmetric architecture in the lipid bilayer membranes, and (iii) direct the water-in-oil emulsions across the oil-water interface of an oscillating oil jet in a co-flowing confined geometry to encapsulate the inner aqueous phase inside a lipid bilayer and complete the fabrication of GUVs. In the first step, we utilize a flow-focusing geometry with precisely controlled pneumatic pressures to form monodisperse water-in-oil emulsions. We observed different regimes in forming water-in-oil multiphase flows by changing the applied pressures and discovered a hysteretic behavior in jet breakup and droplet generation. In the second step of GUV fabrication, an oil stream containing phospholipids carries the emulsions into a separation region where we steer the emulsions across two parallel oil streams using active dielectrophoretic and pinched-flow fractionation separations. We explore the effect of applied DC voltage magnitude and carrier oil stream flow rate on the separation efficiency. We develop an image processing code that measures the degree of mixing between the two oil streams as the water-in-oil emulsions travel across them under dielectrophoretic steering to find the ideal operational conditions. Finally, we utilize an oscillating co-flowing jet to complete the formation of asymmetric giant unilamellar vesicles and transfer them to an aqueous phase. We investigate the effect of flow rates on properties of the co-flowing jet oscillating in the whipping mode (i.e., wavelength and amplitude) and define the phase diagram for the oil-in-water jet. Assays used to probe the lipid bilayer membrane of fabricated GUVs showed that membranes were unilamellar, minimal residual oil remained trapped between the two lipid leaflets, and 83% asymmetry was achieved across the lipid bilayers of GUVs.
Drainage of interstitial fluid from the brain occurs via the intramural periarterial drainage (IPAD) pathways along the basement membranes of cerebral capillaries and arteries against the direction of blood flow into the brain. The cerebrovascular smooth muscle cells (SMCs) provide the motive force for driving IPAD, and their decrease in function may explain the deposition of amyloid-beta as cerebral amyloid angiopathy (CAA), a key feature of Alzheimer's disease. The α-adrenoceptor subtype α1A is abundant in the brain, but its distribution in the cerebral vessels is unclear. We analysed cultured human cerebrovascular SMCs and young, old and CAA human brains for (a) the presence of α1A receptor and (b) the distribution of the α1A receptor within the cerebral vessels. The α1A receptor was present on the wall of cerebrovascular SMCs. No significant changes were observed in the vascular expression of the α1A-adrenergic receptor in young, old and CAA cases. The pattern of vascular staining appeared less punctate and more diffuse with ageing and CAA. Our results show that the α1A-adrenergic receptor is preserved in cerebral vessels with ageing and in CAA and is expressed on cerebrovascular smooth muscle cells, suggesting that vascular adrenergic receptors may hold potential for therapeutic targeting of IPAD.
The double-membrane cellular envelope of Gram-negative bacteria enables them to endure harsh environments and represents a barrier to many clinically available antibiotics. The outer membrane (OM) is exposed to the environment and is the first point of contact involved in bacterial processes such as signaling, pathogenesis, and motility. As in the cytoplasmic membrane, the OM in Gram-negative bacteria has a phospholipid-rich inner leaflet and an outer leaflet that is predominantly composed of lipopolysaccharide (LPS). We report on a microfluidic technique for fabricating monodisperse asymmetric giant unilamellar vesicles (GUVs) possessing the Gram-negative bacterial OM lipid composition. Our continuous microfluidic fabrication technique generates 50-150 µm diameter water-in-oil-in-water double emulsions at high-throughput. The water-oil and oil-water interfaces facilitate the self-assembly of phospholipid and LPS molecules to create the inner and outer leaflets of the lipid bilayer, respectively. The double emulsions have ultrathin oil shells, which minimizes the amount of residual organic solvent that remains trapped between the leaflets of the GUV membrane. An extraction process by ethanol and micropipette aspiration of the ultrathin oil shells triggers an adhesive interaction between the two lipid monolayers assembled on the water-oil and oil-water interfaces (i.e., dewetting transition), forcing them to contact and form a lipid bilayer membrane. The effect of different inner-leaflet lipid compositions on the emulsion/vesicle stability and the dewetting transition is investigated. We also report on the values for bending and area expansion moduli of synthetic asymmetric model membranes with lipid composition/architecture that is physiologically relevant to the OM in Pseudomonas aeruginosa bacteria.
The failure to clear amyloid-Beta from an aging brain leads to its accumulation within the walls of arteries and potentially to Alzheimer's disease. However, the clearance mechanism through the intramural periarterial pathway is not well understood. We previously proposed a hydrodynamic reverse transport model for the cerebral arterial basement membrane pathway. In our model, solute transport results from fluidic forcing driven by the superposition of forward and reverse propagating boundary waves. The aim of this study is to experimentally validate this hydrodynamic reverse transport mechanism in a microfluidic device where reverse transport in a rectangular conduit is driven by applying waveforms along its boundaries. Our results support our theory that while the superimposed boundary waves propagate in the forward direction, a reverse flow in the rectangular conduit can be induced by boundary wave reflections. We quantified the fluid transport velocity and direction under various boundary conditions and analyzed numerical simulations that support our experimental findings. We identified a set of boundary wave parameters that achieved reverse transport, which could be responsible for intramural periarterial drainage of cerebral metabolic waste.
We report on the use of electrospray atomization to deliver nanoparticles and surfactant directly to the surface of sessile droplets. The particles delivered to the target droplet remained adsorbed at its interface since they arrived solvent-free. Upon complete evaporation, the interface of the target drop was mapped to the underlying substrate, forming a nanoparticle deposit. The use of electrospray permitted the exploration of the interfacial particle transport and the role of surfactants in governing particle motion and deposit structure. When no surfactant was present in the sprayed solution, there was no observable convection of the interfacial particles. When Tween 80, a high-molecular-weight surfactant, was added to the sprayed solution, the surface flow was similarly suppressed. Only when small surfactants (e.g., sodium dodecyl sulfate) were present in the sprayed solution was Marangoni flow, directed toward the droplet apex, induced at the interface. This flow drove the interfacial particles to the apex of the target droplet, creating a particle-dense region at the center of the final deposit. We found that small surfactants were capable of desorbing from the interface at a sufficiently high rate relative to the evaporation time scale of the target droplet. Once inside the drop, the desorbed surfactant was convected to the contact line where it accumulated, inducing a surface tension gradient and a solutal Marangoni flow. Numerical modeling using the lattice Boltzmann-Brownian dynamics method confirmed this mechanism of particle transport and its relationship to deposit structure. The use of sacrificial targets combined with electrospray may provide a unique capability for building colloidal monolayers with organized structure in a scalable way.
Synthetic lipid vesicles have served as important model systems to study cellular membrane biology. Research has shown that the mechanical properties of bilayer membranes significantly affects their biological behavior. The properties of a lipid bilayer are governed by lipid acyl chain length, headgroup type, and the presence of membrane proteins. However, few studies have explored how membrane architecture, in particular trans-bilayer lipid asymmetry, influences membrane mechanical properties. In this study, we investigated the effects of lipid bilayer architecture (i.e. asymmetry) on the mechanical properties of biological membranes. This was achieved using a customized micropipette aspiration system and a novel microfluidic technique previously developed by our team for building asymmetric phospholipid vesicles with tailored bilayer architecture. We found that the bending modulus and area expansion modulus of the synthetic asymmetric bilayers were up to 50% larger than the values acquired for symmetric bilayers. This was caused by the dissimilar lipid distribution in each leaflet of the bilayer for the asymmetric membrane. To the best of our knowledge, this is the first report on the impact of trans-bilayer asymmetry on the area expansion modulus of synthetic bilayer membranes. Since the mechanical properties of bilayer membranes play an important role in numerous cellular processes, these results have significant implications for membrane biology studies.
Cell Membrane/chemistry , Lipid Bilayers/chemistry , Membrane Proteins/chemistry , Phospholipids/chemistry , Biomechanical Phenomena
We report on a novel microfluidic strategy for the continuous fabrication of monodisperse asymmetric vesicles with customized membrane composition, size, and luminal content. The microfluidic device encompasses a triangular post region and two flow-focusing regions. The major steps involved in the vesicle fabrication process include: (1) forming highly uniform water emulsions in an oil/inner-leaflet-lipid solution, (2) replacing the inner-leaflet-lipid solution with an outer-leaflet-lipid solution inside the microchannel network, (3) forming water-in-oil-in-water double emulsions, and (4) extracting excess oil/outer-leaflet-lipid solution from the double emulsions. Bilayer membrane asymmetry and unilamellarity are evaluated using a fluorescence quenching assay and a transmembrane protein insertion assay, respectively. Our approach addresses many of the deficiencies found in existing technologies for building vesicles, and yields strong membrane asymmetry. The ability to create and sustain membrane asymmetry is an important feature, as it is a characteristic of nearly all natural membranes. Over 80% of the vesicles remain stable for at least 6 weeks and the membrane asymmetry is maintained for over 30 hours. The asymmetric vesicles built using this strategy are collected off-chip and hold the potential to be used as model systems in membrane biology or as vehicles for drug delivery.
Membranes, Artificial , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Models, Biological , Cell Membrane/chemistry , Emulsions/chemistry , Equipment Design , Fluorescent Dyes , Membrane Lipids/chemistry
A novel tubular ultrasonic motor is presented that uses only a single vibration bending mode of a piezoelectric tube to generate rotation. When the piezoelectric tube bends, the diagonal motion of points on selected areas at the ends of the tube generates forces with tangential components along the same circumferential direction, driving the rotors to rotate. Bi-directional motion is achieved by simply switching the direction of bending. Because only one vibration mode is used, the motor requires only one driving signal and no vibration mode coupling is needed, simplifying the design, fabrication, assembly, and operation of the device. Two prototypes [one with cut-in lead zirconate titanate (PZT) teeth and one with added metal teeth] were built and tested using PZT tubes available to the authors. The tubes have an outside diameter of 6.6 mm, inner diameter of 5.0 mm, and length of 25.4 mm. The working frequencies of the two motors are 27.6 and 23.5 kHz. The motors achieved a maximum no-load speed of 400 rpm and a stall torque of 300 µN·m.
