Matrix Adhesion Polarizes Heart Progenitor Induction In The Invertebrate Chordate Ciona Intestinalis

Cell-matrix adhesion strongly influences developmental signaling. Resulting impacts on cell migration and tissue morphogenesis are well characterized. However, the in vivo impact of adhesion on fate induction remains ambiguous. Here, we employ the invertebrate chordate Ciona intestinalis to delineate an essential in vivo role for matrix adhesion in heart progenitor induction. In Ciona pre-cardiac founder cells, invasion of the underlying epidermis promotes localized induction of the heart progenitor lineage. We found that these epidermal invasions are associated with matrix adhesion along the pre-cardiac cell/epidermal boundary. Through targeted manipulations of RAP GTPase activity, we were able to manipulate pre-cardiac cell-matrix adhesion. Targeted disruption of pre-cardiac cell-matrix adhesion blocked heart progenitor induction. Conversely, increased matrix adhesion generated expanded induction. We were also able to selectively restore cell-matrix adhesion and heart progenitor induction through targeted expression of Ci-Integrin β2. These results indicate that matrix adhesion functions as a necessary and sufficient extrinsic cue for regional heart progenitor induction. Furthermore, time-lapse imaging suggests that cytokinesis acts as an intrinsic temporal regulator of heart progenitor adhesion and induction. Our findings highlight a potentially conserved role for matrix adhesion in early steps of vertebrate heart progenitor specification

Selective Desensitization of Growth Factor Signaling by Cell Adhesion to Fibronectin

Cell adhesion to the extracellular matrix is required to execute growth factor (GF)-mediated cell behaviors, such as proliferation. A major underlying mechanism is that cell adhesion enhances GF-mediated intracellular signals, such as extracellular signal-regulated kinase (Erk). However, because GFs use distinct mechanisms to activate Ras-Erk signaling, it is unclear whether adhesion-mediated enhancement of Erk signaling is universal to all GFs. We examined this issue by quantifying the dynamics of Erk signaling induced by epidermal growth factor, basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) in NIH-3T3 fibroblasts. Adhesion to fibronectin-coated surfaces enhances Erk signaling elicited by epidermal growth factor but not by bFGF or PDGF. Unexpectedly, adhesion is not always a positive influence on GF-mediated signaling. At critical subsaturating doses of PDGF or bFGF, cell adhesion ablates Erk signaling; that is, adhesion desensitizes the cell to GF stimulation, rendering the signaling pathway unresponsive to GF. Interestingly, the timing of growth factor stimulation proved critical to the desensitization process. Erk activation significantly improved only when pre-exposure to adhesion was completely eliminated; thus, concurrent stimulation by GF and adhesion was able to partially rescue adhesion-mediated desensitization of PDGF- and bFGF-mediated Erk and Akt signaling. These findings suggest that adhesion-mediated desensitization occurs with rapid kinetics and targets a regulatory point upstream of Ras and proximal to GF receptor activation. Thus, adhesion-dependent Erk signaling is not universal to all GFs but, rather, is GF-specific with quantitative features that depend strongly on the dose and timing of GF exposure

The Problem of Adhesion Methods and Locomotion Mechanism Development for Wall-Climbing Robots

This review considers a problem in the development of mobile robot adhesion methods with vertical surfaces and the appropriate locomotion mechanism design. The evolution of adhesion methods for wall-climbing robots (based on friction, magnetic forces, air pressure, electrostatic adhesion, molecular forces, rheological properties of fluids and their combinations) and their locomotion principles (wheeled, tracked, walking, sliding framed and hybrid) is studied. Wall-climbing robots are classified according to the applications, adhesion methods and locomotion mechanisms. The advantages and disadvantages of various adhesion methods and locomotion mechanisms are analyzed in terms of mobility, noiselessness, autonomy and energy efficiency. Focus is placed on the physical and technical aspects of the adhesion methods and the possibility of combining adhesion and locomotion methods

Inhibition of tumor necrosis factor α–stimulated monocyte adhesion to human aortic endothelial cells by AMP-activated protein kinase

<b>Objective</b>— Proatherosclerotic adhesion of leukocytes to the endothelium is attenuated by NO. As AMP-activated protein kinase (AMPK) regulates endothelial NO synthesis, we investigated the modulation of adhesion to cultured human aortic endothelial cells (HAECs) by AMPK. <b>Methods and Results</b>— HAECs incubated with the AMPK activator, AICAR, or expressing constitutively active AMPK demonstrated reduced TNF α-stimulated adhesion of promonocytic U-937 cells. Rapid inhibition of TNF α-stimulated U-937 cell adhesion by AICAR was NO-dependent, associated with unaltered cell surface adhesion molecule expression, and reduced MCP-1 secretion by HAECs. In contrast, inhibition of TNF α-stimulated U-937 cell adhesion by prolonged AMPK activation was NO-independent and associated with reduced cell surface adhesion molecule expression. <b>Conclusions</b>— AMPK activation in HAECs inhibits TNF α-stimulated leukocyte adhesion by a rapid NO-dependent mechanism associated with reduced MCP-1 secretion and a late NO-independent mechanism whereby adhesion molecule expression, in particular E-selectin, is suppressed. We investigated the functional effects of AMPK activation in cultured human endothelial cells. Stimulation of AMPK inhibited TNF α-stimulated monocyte adhesion by two distinct mechanisms: a rapid NO-dependent mechanism associated with a reduction in chemokine release and a late NO-independent mechanism whereby adhesion molecule expression is suppressed

Nucleation of membrane adhesions

Recent experimental and theoretical studies of biomimetic membrane adhesions [Bruinsma et al., Phys. Rev. E 61, 4253 (2000); Boulbitch et al., Biophys. J. 81, 2743 (2001)] suggested that adhesion mediated by receptor interactions is due to the interplay between membrane undulations and a double-well adhesion potential, and should be a first-order transition. We study the nucleation of membrane adhesion by finding the minimum-energy path on the free energy surface constructed from the bending free energy of the membrane and the double-well adhesion potential. We find a nucleation free energy barrier around 20kBT for adhesion of flexible membranes, which corresponds to fast nucleation kinetics with a time scale of the order of seconds. For cell membranes with a larger bending rigidity due to the actin network, the nucleation barrier is higher and may require active processes such as the reorganization of the cortex network to overcome this barrier. Our scaling analysis suggests that the geometry of the membrane shapes of the adhesion contact is controlled by the adhesion length that is determined by the membrane rigidity, the barrier height, and the length scale of the double-well potential, while the energetics of adhesion is determined by the depths of the adhesion potential. These results are verified by numerical calculations

Twin disc assessment of wheel/rail adhesion

Loss of adhesion between a railway wheel and the track has implications for both braking and traction. Poor adhesion in braking is a safety issue as it leads to extended stopping distances. In traction, it is a performance issue as it may lead to reduced acceleration which could cause delays. In this work, wheel/rail adhesion was assessed using a twin disc simulation. The effects of a number of contaminants, such as oil, dry and wet leaves and sand were investigated. These have been shown in the past to have significant effect on adhesion, but this has not been well quantified. The results have shown that both oil and water reduce adhesion from the dry condition. Leaves, however, gave the lowest adhesion values, even when dry. The addition of sand, commonly used as a friction enhancer, to leaves, brought adhesion levels back to the levels without leaves present. Adhesion levels recorded, particularly for the wet, dry and oil conditions are in the range seen in field measurements. Relatively severe disc surface damage and subsurface deformation was seen after the addition of sand. Leaves were also seen to cause indents in the disc surfaces. The twin disc approach has been shown to provide a good approach for comparing adhesion levels under a range of wheel/rail contact conditions, with and without contaminants

Adhesion attenuation and enhancement in aqueous solutions

When two surfaces confine water layers between them at the nanoscale, the behaviour of these confined water molecules can deviate significantly from the behaviour of bulk water, and it could reflect on the adhesion of such surfaces. This study assesses the role of confined water layers on the adhesion of hydrophilic surfaces and how sensitive this adhesion is to the presence of contaminants. Our methodology used atomic force microscopy adhesion measurements, whereby an alumina-sputtered sphere-tipped cantilever was interacted versus a flat alumina single crystal. Testing was performed under immersed conditions using (i) water, (ii) water/dimethylformamide mixtures, (iii) water/ethanol mixtures, and (iv) water/formamide mixtures. These solutions were intended to assess the influence of dielectric constant, molecule size, and the number of hydrogen bonding opportunities available to molecules upon confinement between surfaces. It was found that dilute concentrations of ethanol and formamide decreased the adhesion. In contrast, the adhesion increased in the presence of dilute concentrations of dimethylformamide. The adhesion was attenuated by in excess of two orders of magnitude for high concentrations of the organic solutes

Biomimetic emulsions reveal the effect of homeostatic pressure on cell-cell adhesion

Cell-cell contacts in tissues are continuously subject to mechanical forces due to homeostatic pressure and active cytoskeleton dynamics. While much is known about the molecular pathways of adhesion, the role of mechanics is less well understood. To isolate the role of pressure we present a dense packing of functionalized emulsion droplets in which surface interactions are tuned to mimic those of real cells. By visualizing the microstructure in 3D we find that a threshold compression force is necessary to overcome electrostatic repulsion and surface elasticity and establish protein-mediated adhesion. Varying the droplet interaction potential maps out a phase diagram for adhesion as a function of force and salt concentration. Remarkably, fitting the data with our theoretical model predicts binder concentrations in the adhesion areas that are similar to those found in real cells. Moreover, we quantify the adhesion size dependence on the applied force and thus reveal adhesion strengthening with increasing homeostatic pressure even in the absence of active cellular processes. This biomimetic approach reveals the physical origin of pressure-sensitive adhesion and its strength across cell-cell junctions.Comment: 20 pages, 5 figure

Platelet-collagen adhesion: evidence for participation of antigenically distinct entities.

Univalent antibody fragments prepared from a rabbit antiserum raised against whole human platelets completely inhibited adhesion of platelets to immobilized trimeric collagen in a defined, Mg2+-dependent, adhesion assay. An octylglucoside extract of whole platelets completely neutralized this antibody, and all neutralizing activity bound to immobilized wheat germ agglutinin. Further fractionation on concanavalin A gave rise to subfractions that each neutralized only partially at saturation, when tested against antibody concentrations that inhibit 50% of platelet-collagen adhesion. When tested against higher antibody concentrations that completely inhibited adhesion, each subfraction had no detectable neutralizing effect, although the combined subfractions neutralized completely. This and other evidence suggests that more than one platelet entity participates in platelet-collagen adhesion. Although distinct, they appear to play interdependent roles in a single adhesion process