High-resolution near-wall fluorescent microparticle image velocimetry (micro-PIV) was used in mouse cremaster muscle venules in vivo to measure velocity profiles in the red cell-depleted plasma layer near the endothelial lining. micro-PIV data of the instantaneous translational speeds and radial positions of fluorescently labeled microspheres (0.47 microm) in an optical section through the midsagittal plane of each vessel were used to determine fluid particle translational speeds. Regression of a linear velocity distribution based on near-wall fluid-particle speeds consistently revealed a negative intercept when extrapolated to the vessel wall. Based on a detailed three-dimensional analysis of the local fluid dynamics, we estimate a mean effective thickness of approximately 0.33 micro m for an impermeable endothelial surface layer or approximately 0.44 micro m assuming the lowest hydraulic resistivity of the layer that is consistent with the observed particle motions. The extent of plasma flow retardation through the layer required to be consistent with our micro-PIV data results in near complete attenuation of fluid shear stress on the endothelial-cell surface. These findings confirm the presence of a hydrodynamically effective endothelial surface layer, and emphasize the need to revise previous concepts of leukocyte adhesion, stress transmission to vascular endothelium, permeability, and mechanotransduction mechanisms.

We show that many salient hemodynamic flow properties, which have been difficult or impossible to assess in microvessels in vivo, can be estimated by using microviscometry and fluorescent microparticle image velocimetry in microvessels >20 μm in diameter. Radial distributions in blood viscosity, shear stress, and shear rate are obtained and used to predict axial pressure gradient, apparent viscosity, and endothelial-cell surface-layer thickness in vivo. Based solely on microparticle image velocimetry data, which are readily obtainable during the course of most intravital microscopy protocols from systemically injected particle tracers, we show that the microviscometric method consistently predicted a reduction in local and apparent blood viscosity after isovolemic hemodilution. Among its clinical applications, hemodilution is a procedure that is used to treat various pathologies that require reduction in peripheral vascular-flow resistance. Our results are directly relevant in this context because they suggest that the fractional decrease in systemic hematocrit is ≈25–35% greater than the accompanying fractional decrease in microvascular-flow resistance in vivo. In terms of its fundamental usefulness, the microviscometric method provides a comprehensive quantitative analysis of microvascular hemodynamics that has applications in broad areas of medicine and physiology and is particularly relevant to quantitative studies of angiogenesis, tumor growth, leukocyte adhesion, vascular-flow resistance, tissue perfusion, and endothelial-cell mechanotransduction

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An approach is presented that uses velocimetry data to estimate accurately the spatial distribution of viscosity in steady laminar parallel flows of incompressible linearly viscous fluids. The approach is generally applicable to Newtonian fluids with spatially varying viscosity or to particle-suspension flows where a non-uniform distribution of the particles contributes to spatial variations in the local effective viscosity of the suspension. Emphasis is placed on the application of these methods to steady axisymmetric blood flow in cylindrical glass capillary tubes and microvessels. In this context, the spatial variations in viscosity over the vessel cross-section are predicted where it is assumed that the rheological properties associated with a heterogeneous red blood cell suspension can be well approximated by a continuous generalized linearly viscous fluid having a spatially non-uniform viscosity. For such a fluid, an expression for the viscosity profile over the vessel cross-section is derived that satisfies the conservation principles of mass and momentum and depends upon the a priori determined velocity distribution, which is extracted from fluorescent micro-particle image velocimetry data obtained from microvessels in vivo. These profiles provide useful information about dynamic, kinematic and rheological properties of the flow that include expressions for the axial pressure-gradient component, the local shear stress distribution, and the relative apparent viscosity. In microvessels, the effect of the glycocalyx surface layer on the vessel wall is also accounted for in the analysis by modelling the layer as a uniformly thick porous medium. Velocimetry data are presented from in vivo measurements made in venules after the application of a light-dye treatment to degrade the glycocalyx. Results reveal that these methods are sufficiently sensitive to detect a reduction in glycocalyx thickness of ∼ 0.3 µm, which represents a fractional decrease in thickness of ∼ 60-70% when compared with results from a separately published data set obtained from venules having an intact glycocalyx.

Seismic reflection profiles show at least four major mass-transport deposits (MTDs) on the Amazon Fan that drilling has shown date from the late Pleistocene. Each deposit extends over an area on the order of 10 4 km 2 and is 50-100 m thick. The entire thickness of individual MTDs was penetrated at Sites 931, 933, 935, 936, 941, and 944, and wireline logs were collected at most of these sites. Most deposits consist of large deformed blocks (meters to decameters) of clayey sediment. A little matrix is recognized between blocks, and some weaker smaller blocks are highly deformed. Thin matrix-rich deposits with small clasts near the top of some units are true debris flows. Properties of clasts in the MTDs show a broadly repetitive character vertically within the deposit, on a scale of meters to tens of meters. There is no evidence that a long time span is represented by discontinuities in sediment properties; rather, this repetitive pattern probably represents retrogressive failure from a headwall scarp. Major units 20-50 m thick within the MTDs can be correlated between sites. Sediment properties and microfossils suggest that most sediment was derived from muddy channel-levee deposits on the continental slope, but some sediment (particularly near the base of flows) resembles local deep-water levee sediments. Mass-transport events are inferred to have initiated in slope and upper-fan levee sediments. This sediment was underconsolidated because of rapid prodeltaic deposition during marine lowstands as well as a result of the presence of shallow gas and gas hydrates. Local steepening and weakening by diapiric intrusion may also have facilitated failure. The ages of the mass-transport events may correlate with times of falling sea level, when gas hydrate sublimation could destabilize sediments. MTDs were partly confined by pre-existing channel-levee topography on the fan. In places, high-relief levee deposits were eroded by the mass-transport flow and incorporated in the basal part of the deposit.

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BackgroundMammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. The nucleus must be stiff enough to withstand cytoskeletal forces, but flexible enough to remodel as the cell changes shape. This is particularly important for cells migrating through confined spaces, where the nuclear shape must change in order to fit through a constriction. This occurs many times in the life cycle of a neutrophil, which must protect its chromatin from damage and disruption associated with migration. Here we characterized the effects of constricted migration in neutrophil-like cells.ResultsTotal RNA sequencing identified that migration of neutrophil-like cells through 5- or 14-μm pores was associated with changes in the transcript levels of inflammation and chemotaxis-related genes when compared to unmigrated cells. Differentially expressed transcripts specific to migration with constriction were enriched for groups of genes associated with cytoskeletal remodeling.Hi-C was used to capture the genome organization in control and migrated cells. Limited switching was observed between the active (A) and inactive (B) compartments after migration. However, global depletion of short-range contacts was observed following migration with constriction compared to migration without constriction. Regions with disrupted contacts, TADs, and compartments were enriched for inactive chromatin.ConclusionShort-range genome organization is preferentially altered in inactive chromatin, possibly protecting transcriptionally active contacts from the disruptive effects of migration with constriction. This is consistent with current hypotheses implicating heterochromatin as the mechanoresponsive form of chromatin. Further investigation concerning the contribution of heterochromatin to stiffness, flexibility, and protection of nuclear function will be important for understanding cell migration in relation to human health and disease.Electronic supplementary materialThe online version of this article (10.1186/s12915-018-0608-2) contains supplementary material, which is available to authorized users.

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