Flow-accelerated platelet biogenesis is due to an elasto-hydrodynamic instability.

Blood platelets are formed by fragmentation of long membrane extensions from bone marrow megakaryocytes in the blood flow. Using lattice-Boltzmann/immersed boundary simulations we propose a biological Rayleigh-Plateau instability as the biophysical mechanism behind this fragmentation process. This instability is akin to the surface tension-induced breakup of a liquid jet but is driven by active cortical processes including actomyosin contractility and microtubule sliding. Our fully three-dimensional simulations highlight the crucial role of actomyosin contractility, which is required to trigger the instability, and illustrate how the wavelength of the instability determines the size of the final platelets. The elasto-hydrodynamic origin of the fragmentation explains the strong acceleration of platelet biogenesis in the presence of an external flow, which we observe in agreement with experiments. Our simulations then allow us to disentangle the influence of specific flow conditions: While a homogeneous flow with uniform velocity leads to the strongest acceleration, a shear flow with a linear velocity gradient can cause fusion events of two developing platelet-sized swellings during fragmentation. A fusion event may lead to the release of larger structures which are observable as preplatelets in experiments. Together, our findings strongly indicate a mainly physical origin of fragmentation and regulation of platelet size in flow-accelerated platelet biogenesis.

Red blood cell shape transitions and dynamics in time-dependent capillary flows.

The dynamics of single red blood cells (RBCs) determine microvascular blood flow by adapting their shape to the flow conditions in the narrow vessels. In this study, we explore the dynamics and shape transitions of RBCs on the cellular scale under confined and unsteady flow conditions using a combination of microfluidic experiments and numerical simulations. Tracking RBCs in a comoving frame in time-dependent flows reveals that the mean transition time from the symmetric croissant to the off-centered, nonsymmetric slipper shape is significantly faster than the opposite shape transition, which exhibits pronounced cell rotations. Complementary simulations indicate that these dynamics depend on the orientation of the RBC membrane in the channel during the time-dependent flow. Moreover, we show how the tank-treading movement of slipper-shaped RBCs in combination with the narrow channel leads to oscillations of the cell's center of mass. The frequency of these oscillations depends on the cell velocity, the viscosity of the surrounding fluid, and the cytosol viscosity. These results provide a potential framework to identify and study pathological changes in RBC properties.

Vortical flow structures induced by red blood cells in capillaries.

OBJECTIVE: Knowledge about the flow field of the plasma around the red blood cells in capillary flow is important for a physical understanding of blood flow and the transport of micro- and nanoparticles and molecules in the flowing plasma. We conducted an experimental study on the flow field around red blood cells in capillary flow that is complemented by simulations of vortical flow between red blood cells. METHODS: Red blood cells were injected in a 10 × 12 µm rectangular microchannel at a low hematocrit, and the flow field around one or two cells was captured by a high-speed camera that tracked 250 nm nanoparticles in the flow field, acting as tracers. RESULTS: While the flow field around a steady "croissant" shape is found to be similar to that of a rigid sphere, the flow field around a "slipper" shape exhibits a small vortex at the rear of the red blood cell. Even more pronounced are vortex-like structures observed in the central region between two neighboring croissants. CONCLUSIONS: The rotation frequency of the vortices is to a good approximation, inversely proportional to the distance between the cells. Our experimental data are complemented by numerical simulations.

Precise 2D-Patterned Incompatible Catalysts for Reactions in One-Pot.

Precise and direct two-dimensional (2D) printing of the incompatible polymer acid-base catalysts and their utility in one-pot two-step reactions were shown. Multistep catalytic reactions using incompatible catalysts in a one-pot reaction cascade requires special methods and materials to isolate the catalysts from each other. In general, this is a tedious process requiring special polymer architectures as the carrier for the catalysts to preserve the activity of otherwise incompatible catalysts. We propose the immobilization of incompatible polymer catalysts, such as polymer acid and base catalysts, on a substrate in variable sizes and amounts by precise 2D printing. The terpolymers with basic (4-vinylpyridine) and acidic (styrene sulfonic acid) functionalities and methacryloyl benzophenone as a UV cross-linking unit were used for 2D printing on poly(ethylene terephthalate) (PET). The printed meshes were immersed together in a reaction solution containing (dimethoxymethyl)benzene and ethyl cyanoformate, resulting in a two-step acid-base catalyzed cascade reaction; that is, deacetalization followed by carbon-building reaction. The time-dependent consumption of (dimethoxymethyl)benzene to the intermediate benzaldehyde and the product was monitored, and a kinetic model was developed to investigate the underlying reaction dynamics. The complexity of multistep Wolf-Lamb-type reactions was generally significantly decreased by using our approach because of the easy polymerization and immobilization procedure.

Wolf-Lamb-type Catalysis in One Pot Using Electrospun Polymeric Catalyst Membranes.

Multistep catalytic transformations using incompatible catalysts (Wolf-Lamb-type) in a one-pot reaction cascade require site isolation of different catalysts by compartmentalization. In this work, the use of different electrospun catalytic membranes in a modular way as individual compartments is shown for one-pot Wolf-Lamb-type reaction cascades. The data are presented for one-pot cascade reaction sequences catalyzed by acidic and basic membranes made by electrospinning polymeric acid (poly(styrene-co-styrene sulfonic acid-co-4-methacryloyl-oxybenzophen)) and basic (poly(styrene-co-4-vinylpyridine-co-4-methacryloyl-oxybenzophen)) catalysts, respectively. The two-step, one-pot system used is the acidic catalyzed deacetylation of dimethoxybenzylacetale to benzaldehyde, which reacts with ethyl cyanoformate to result in a high yield of product (over 90%) under base-catalyzed conditions. The reaction kinetics are further monitored and evaluated by using differential equations, showing the necessity of a parameter Δt to represent a retarded start for the second reaction step. The concept provides an easy and upscalable approach for use in Wolf-Lamb-type systems.

Antimargination of Microparticles and Platelets in the Vicinity of Branching Vessels.

We investigate the margination of microparticles/platelets in blood flow through complex geometries typical for in vivo vessel networks: a vessel confluence and a bifurcation. Using three-dimensional lattice Boltzmann simulations, we confirm that behind the confluence of two vessels, a cell-free layer devoid of red blood cells develops in the channel center. Despite its small size of roughly 1 µm, this central cell-free layer persists for up to 100 µm after the confluence. Most importantly, we show from simulations that this layer also contains a significant amount of microparticles/platelets and validate this result by in vivo microscopy in mouse venules. At bifurcations, however, a similar effect does not appear, and margination is largely unaffected by the geometry. This antimargination toward the vessel center after a confluence may explain earlier in vivo observations, which found that platelet concentrations near the vessel wall are seen to be much higher on the arteriolar side (containing bifurcations) than on the venular side (containing confluences) of the vascular system.

Parallel and Perpendicular Alignment of Anisotropic Particles in Free Liquid Microjets and Emerging Microdroplets.

Liquid microjets play a key role in fiber spinning, inkjet printing, and coating processes. In all of these applications, the liquid jets carry dispersed particles whose spatial and orientational distributions within the jet critically influence the properties of the fabricated structures. Despite its importance, there is currently no knowledge about the orientational distribution of particles within microjets and droplets. Here, we demonstrate a microfluidic device that allows to determine the local particle distribution and orientation by X-ray scattering. Using this methodology, we discovered unexpected changes in the particle orientation upon exiting the nozzle to form a free jet, and upon jet break-up into droplets, causing an unusual biaxial particle orientation. We show how flow and aspect ratio determine the flow orientation of anisotropic particles. Furthermore, we demonstrate that the observed phenomena are a general characteristic of anisotropic particles. Our findings greatly enhance our understanding of particle orientation in free jets and droplets and provide a rationale for controlling particle alignment in liquid jet-based fabrication methodologies.

Numerical-experimental observation of shape bistability of red blood cells flowing in a microchannel.

Red blood cells flowing through capillaries assume a wide variety of different shapes owing to their high deformability. Predicting the realized shapes is a complex field as they are determined by the intricate interplay between the flow conditions and the membrane mechanics. In this work we construct the shape phase diagram of a single red blood cell with a physiological viscosity ratio flowing in a microchannel. We use both experimental in vitro measurements as well as 3D numerical simulations to complement the respective other one. Numerically, we have easy control over the initial starting configuration and natural access to the full 3D shape. With this information we obtain the phase diagram as a function of initial position, starting shape and cell velocity. Experimentally, we measure the occurrence frequency of the different shapes as a function of the cell velocity to construct the experimental diagram which is in good agreement with the numerical observations. Two different major shapes are found, namely croissants and slippers. Notably, both shapes show coexistence at low (<1 mm s-1) and high velocities (>3 mm s-1) while in-between only croissants are stable. This pronounced bistability indicates that RBC shapes are not only determined by system parameters such as flow velocity or channel size, but also strongly depend on the initial conditions.

Brownian motion near an elastic cell membrane: A theoretical study.

Elastic confinements are an important component of many biological systems and dictate the transport properties of suspended particles under flow. In this paper, we review the Brownian motion of a particle moving in the vicinity of a living cell whose membrane is endowed with a resistance towards shear and bending. The analytical calculations proceed through the computation of the frequency-dependent mobility functions and the application of the fluctuation-dissipation theorem. Elastic interfaces endow the system with memory effects that lead to a long-lived anomalous subdiffusive regime of nearby particles. In the steady limit, the diffusional behavior approaches that near a no-slip hard wall. The analytical predictions are validated and supplemented with boundary-integral simulations.

Creeping motion of a solid particle inside a spherical elastic cavity⋆.

On the basis of the linear hydrodynamic equations, we present an analytical theory for the low-Reynolds-number motion of a solid particle moving inside a larger spherical elastic cavity which can be seen as a model system for a fluid vesicle. In the particular situation where the particle is concentric with the cavity, we use the stream function technique to find exact analytical solutions of the fluid motion equations on both sides of the elastic cavity. In this particular situation, we find that the solution of the hydrodynamic equations is solely determined by membrane shear properties and that bending does not play a role. For an arbitrary position of the solid particle within the spherical cavity, we employ the image solution technique to compute the axisymmetric flow field induced by a point force (Stokeslet). We then obtain analytical expressions of the leading-order mobility function describing the fluid-mediated hydrodynamic interactions between the particle and the confining elastic cavity. In the quasi-steady limit of vanishing frequency, we find that the particle self-mobility function is higher than that predicted inside a rigid no-slip cavity. Considering the cavity motion, we find that the pair-mobility function is determined only by membrane shear properties. Our analytical predictions are supplemented and validated by fully resolved boundary integral simulations where a very good agreement is obtained over the whole range of applied forcing frequencies.

Hydrodynamic coupling and rotational mobilities near planar elastic membranes.

We study theoretically and numerically, the coupling and rotational hydrodynamic interactions between spherical particles near a planar elastic membrane that exhibits resistance toward shear and bending. Using a combination of the multipole expansion and Faxén's theorems, we express the frequency-dependent hydrodynamic mobility functions as a power series of the ratio of the particle radius to the distance from the membrane for the self mobilities and as a power series of the ratio of the radius to the interparticle distance for the pair mobilities. In the quasi-steady limit of zero frequency, we find that the shear- and bending-related contributions to the particle mobilities may have additive or suppressive effects depending on the membrane properties in addition to the geometric configuration of the interacting particles relative to the confining membrane. To elucidate the effect and role of the change of sign observed in the particle self mobilities and pair mobilities, we consider an example involving a torque-free doublet of counterrotating particles near an elastic membrane. We find that the induced rotation rate of the doublet around its center of mass may differ in magnitude and direction depending on the membrane shear and bending properties. Near a membrane of only energetic resistance toward shear deformation, such as that of a certain type of elastic capsules, the doublet undergoes rotation of the same sense as observed near a no-slip wall. Near a membrane of only energetic resistance toward bending, such as that of a fluid vesicle, we find a reversed sense of rotation. Our analytical predictions are supplemented and compared with fully resolved boundary integral simulations where very good agreement is obtained over the whole range of applied frequencies.

Strongly Accelerated Margination of Active Particles in Blood Flow.

Synthetic nanoparticles and other stiff objects injected into a blood vessel filled with red blood cells are known to marginate toward the vessel walls. By means of hydrodynamic lattice-Boltzmann simulations, we show that active particles can strongly accelerate their margination by moving against the flow direction: particles located initially in the channel center migrate much faster to their final position near the wall than in the nonactive case. We explain our findings by an enhanced rate of collisions between the stiff particles and the deformable red blood cells. Our results imply that a significantly faster margination can be achieved either technically by the application of an external magnetic field (if the particles are magnetic) or biologically by self-propulsion (if the particles are, e.g., swimming bacteria).

Spatially resolved dielectric constant of confined water and its connection to the non-local nature of bulk water.

We use molecular dynamics simulations to compute the spatially resolved static dielectric constant of water in cylindrical and spherical nanopores as occurring, e.g., in protein water pockets or carbon nanotubes. For this, we derive a linear-response formalism which correctly takes into account the dielectric boundary conditions in the considered geometries. We find that in cylindrical confinement, the axial component behaves similar as the local density akin to what is known near planar interfaces. The radial dielectric constant shows some oscillatory features when approaching the surface if their radius is larger than about 2 nm. Most importantly, however, the radial component exhibits pronounced oscillations at the center of the cavity. These surprising features are traced back quantitatively to the non-local dielectric nature of bulk water.

Hydrodynamic interaction between particles near elastic interfaces.

We present an analytical calculation of the hydrodynamic interaction between two spherical particles near an elastic interface such as a cell membrane. The theory predicts the frequency dependent self- and pair-mobilities accounting for the finite particle size up to the 5th order in the ratio between particle diameter and wall distance as well as between diameter and interparticle distance. We find that particle motion towards a membrane with pure bending resistance always leads to mutual repulsion similar as in the well-known case of a hard-wall. In the vicinity of a membrane with shearing resistance, however, we observe an attractive interaction in a certain parameter range which is in contrast to the behavior near a hard wall. This attraction might facilitate surface chemical reactions. Furthermore, we show that there exists a frequency range in which the pair-mobility for perpendicular motion exceeds its bulk value, leading to short-lived superdiffusive behavior. Using the analytical particle mobilities we compute collective and relative diffusion coefficients. The appropriateness of the approximations in our analytical results is demonstrated by corresponding boundary integral simulations which are in excellent agreement with the theoretical predictions.

Ion-specific solvation water dynamics: single water versus collective water effects.

Recent femtosecond-resolved spectroscopy experiments demonstrate the single-water orientational dynamics in the first solvation shell around monatomic ions to be slowed down. In contrast, dielectric spectroscopy experiments exhibit a blue shift of the water dielectric relaxation time with rising salt concentration, indicative of faster water dynamics. Using molecular dynamics simulations employing nonpolarizable and thermodynamically optimized ion force fields, we reproduce both experimental trends and resolve these conflicting experimental findings by the simultaneous analysis of single-water and collective-water dynamics in the ion solvation shells. While the single-molecule reorientational dynamics of first solvation shell water around ions indeed slows down, the collective dynamics, which furnishes the dominant contribution to the dielectric response, accelerates. This collective acceleration is rationalized by a dramatically decreasing water cooperativity around ions when compared to bulk water, quantified by the Kirkwood dielectric enhancement factor. The static dielectric decrement of salt solutions is thus reinterpreted as a dielectric structure breaking rather than a water alignment effect. Both the dielectric blue shift and the dielectric decrement become stronger with increasing anion size, meaning larger halide ions such as iodide are more efficient dielectric structure breakers than small halide ions such as fluoride.

Dissecting ion-specific dielectric spectra of sodium-halide solutions into solvation water and ionic contributions.

Using extensive equilibrium molecular dynamics simulations we determine the dielectric spectra of aqueous solutions of NaF, NaCl, NaBr, and NaI. The ion-specific and concentration-dependent shifts of the static dielectric constants and the dielectric relaxation times match experimental results very well, which serves as a validation of the classical and non-polarizable ionic force fields used. The purely ionic contribution to the dielectric response is negligible, but determines the conductivity of the salt solutions. The ion-water cross correlation contribution is negative and reduces the total dielectric response by about 5%-10% for 1 M solutions. The dominating water dielectric response is decomposed into different water solvation shells and ion-pair configurations, by this the spectral blue shift and the dielectric decrement of salt solutions with increasing salt concentration is demonstrated to be primarily caused by first-solvation shell water. With rising salt concentration the simulated spectra show more pronounced deviations from a single-Debye form and can be well described by a Cole-Cole fit, in quantitative agreement with experiments. Our spectral decomposition into ionic and different water solvation shell contributions does not render the individual contributions more Debye-like, this suggests the non-Debye-like character of the dielectric spectra of salt solutions not to be due to the superposition of different elementary relaxation processes with different relaxation times. Rather, the non-Debye-like character is likely to be an inherent spectral signature of solvation water around ions.

Mechanical complexity of living cells can be mapped onto simple homogeneous equivalents.

Biological cells are built up from different constituents of varying size and stiffness which all contribute to the cell's mechanical properties. Despite this heterogeneity, in the analysis of experimental measurements one often assumes a strongly simplified homogeneous cell and thus a single elastic modulus is assigned to the entire cell. This ad-hoc simplification has so far mostly been used without proper justification. Here, we use computer simulations to show that indeed a mechanically heterogeneous cell can effectively be replaced by a homogeneous equivalent cell with a volume averaged elastic modulus. To demonstrate the validity of this approach, we investigate a hyperelastic cell with a heterogeneous interior under compression and in shear/channel flow mimicking atomic force and microfluidic measurements, respectively. We find that the homogeneous equivalent cell reproduces quantitatively the behavior of its heterogeneous counterpart, and that this equality is largely independent of the stiffness or spatial distribution of the heterogeneity.

Nominally identical microplastic models differ greatly in their particle-cell interactions.

Due to the abundance of microplastics in the environment, research about its possible adverse effects is increasing exponentially. Most studies investigating the effect of microplastics on cells still rely on commercially available polystyrene microspheres. However, the choice of these model microplastic particles can affect the outcome of the studies, as even nominally identical model microplastics may interact differently with cells due to different surface properties such as the surface charge. Here, we show that nominally identical polystyrene microspheres from eight different manufacturers significantly differ in their ζ-potential, which is the electrical potential of a particle in a medium at its slipping plane. The ζ-potential of the polystyrene particles is additionally altered after environmental exposure. We developed a microfluidic microscopy platform to demonstrate that the ζ-potential determines particle-cell adhesion strength. Furthermore, we find that due to this effect, the ζ-potential also strongly determines the internalization of the microplastic particles into cells. Therefore, the ζ-potential can act as a proxy of microplastic-cell interactions and may govern adverse effects reported in various organisms exposed to microplastics.

Anomalous anisotropic diffusion dynamics of hydration water at lipid membranes.

The diffusional water dynamics in the hydration layer of a dipalmitoylphosphatidylcholine bilayer is studied using molecular dynamics simulations. By mapping the perpendicular water motion on the ordinary diffusion equation, we disentangle free energetic and friction effects and show that perpendicular diffusion is strongly reduced. The lateral water motion exhibits anomalous diffusion up to several nanoseconds and is characterized by even further decreased diffusion coefficients, which by comparison with coarse-grained simulations are explained by the transient corrugated effective free energy landscape imposed by the lipids. This is in contrast to homogenous surfaces, where boundary hydrodynamic theory quantitatively predicts the anisotropy of water diffusion.

Nanoscale pumping of water by AC electric fields.

Using molecular dynamics simulations we demonstrate pumping of water through a carbon nanotube by time-dependent electric fields. The fields are generated by electrodes with oscillating charges in a broad gigahertz frequency range that are attached laterally to the tube. The key ingredient is a phase shift between the electrodes to break the spatiotemporal symmetry. A microscopic theory based on a polarization-dragging mechanism accounts quantitatively for our numerical findings.