Endothelial adherens junctions maintain vascular integrity. Arteries and veins differ in their permeability but whether organization and strength of their adherens junctions vary has not been demonstrated in vivo. Here we report that vascular endothelial cadherin, an endothelial specific adhesion protein located at adherens junctions, is phosphorylated in Y658 and Y685 in vivo in veins but not in arteries under resting conditions. This difference is due to shear stress-induced junctional Src activation in veins. Phosphorylated vascular endothelial-cadherin is internalized and ubiquitinated in response to permeability-increasing agents such as bradykinin and histamine. Inhibition of Src blocks vascular endothelial cadherin phosphorylation and bradykinin-induced permeability. Point mutation of Y658F and Y685F prevents vascular endothelial cadherin internalization, ubiquitination and an increase in permeability by bradykinin in vitro. Thus, phosphorylation of vascular endothelial cadherin contributes to a dynamic state of adherens junctions, but is not sufficient to increase vascular permeability in the absence of inflammatory agents.

The time required to re-establish a functioning endothelial cell layer after vascular implant placement is critical to the success of the respective cardiologic or surgical intervention. Topographic modifications of implant surfaces promise to expedite endothelial regeneration by triggering the activation of cellular machineries that facilitate cell spreading. Exploiting nanoimprint lithography techniques on cyclic olefin copolymer foils, we engineered biocompatible submicron-and micro-structured gratings with groove and ridge width of 1 or 5 mm and groove depth ranging from 0.1 to 2 mm. Our results reveal that both the onset of endothelial spreading and subsequent texture-guided cell polarization critically depend on the feature size of the underlying topography, yet are independently modulated by the surface texture. Specifically, we demonstrate that on gratings with ridge and groove width of 1 mm and groove depth of 1 mm or deeper, the onset of endothelial spreading is 40% faster than on flat substrates, and that the cells align within ten degrees to the gratings. On this topography, we identify two independently regulated phases: acceleration of the onset of spreading supported by the rapid activation of integrin signaling proceeding via Focal Adhesion Kinase, and contact guidance which requires ROCK1/2 and myosin-II dependent cell contractility and focal adhesion maturation.

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The safe integration of cardiovascular devices requires the sustainable coverage of their luminal surface by endothelial cells (ECs). The engineering of active surface textures has the potential to coordinate cellular adhesion and migration under the action of hemodynamic forces. We define a paradigm to rationally design textures maximizing EC activities as a function of the applied stresses. This is based on harnessing the adhesions established by ECs through fine-tuning of the vertical extend of the underlying surface nanotopography.

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Nanophosphors are light-emitting materials with stable optical properties that represent promising tools for bioimaging. The synthesis of nanophosphors, and thus the control of their surface properties is, however, challenging. Here, flame aerosol technology is exploited to generate Tbactivated Y 2 O 3 nanophosphors (~25 nm) encapsulated in situ by a nano-thin amorphous inert SiO 2 film. The nanocrystalline core exhibits a bright green luminescence following the Tb 3+ ion transitions, while the hermetic SiO 2 -coating prevents any unspecific interference with cellular activities. The SiO 2 -coated nanophosphors display minimal photobleaching upon imaging and can be easily functionalized through surface absorption of biological molecules. Therefore, they can be used as bio-nanoprobes for cell detection and for long-term monitoring of cellular activities. As an example, we report on the interaction between epidermal growth factor (EGF) functionalized nanophosphors and mouse melanoma cells. The cellular uptake of the nanophosphors is visualized with confocal microscopy and the specific activation of EGF receptors (EGFR) is revealed with biochemical techniques. Altogether, our results establish SiO 2 -coated Tb-activated Y 2 O 3 nanophosphors as superior imaging tools for biological applications.

Cell migration is commonly quantified by tracking the speed of the cell layer interface in wound healing assays. This quantification is often hampered by low signal to noise ratio, in particular when complex substrates are employed to emulate in vivo cell migration in geometrically complex environments. Moreover, information about the cell motion, readily available inside the migrating cell layers, is not usually harvested. We introduce Cell Image Velocimetry (CIV), a combination of cell layer segmentation and image velocimetry algorithms, to drastically enhance the quantification of cell migration by wound healing assays. The resulting software analyses the speed of the interface as well as the detailed velocity field inside the cell layers in an automated fashion. CIV is shown to be highly robust for images with low signal to noise ratio, low contrast and frame shifting and it is portable across various experimental settings. The modular design and parametrization of CIV is not restricted to wound healing assays and allows for the exploration and quantification of flow phenomena in any optical microscopy dataset. Here, we demonstrate the capabilities of CIV in wound healing assays over topographically engineered surfaces and quantify the relative merits of differently aligned gratings on cell migration.

We propose a general procedure to construct noncommutative deformations of an algebraic submanifold M of $\mathbb {R}^{n}$ ℝ n , specializing the procedure [G. Fiore, T. Weber, Twisted submanifolds of$\mathbb {R}^{n}$ ℝ n , arXiv:2003.03854] valid for smooth submanifolds. We use the framework of twisted differential geometry of Aschieri et al. (Class. Quantum Grav. 23, 1883–1911, 2006), whereby the commutative pointwise product is replaced by the ⋆-product determined by a Drinfel’d twist. We actually simultaneously construct noncommutative deformations of all the algebraic submanifolds Mc that are level sets of the fa(x), where fa(x) = 0 are the polynomial equations solved by the points of M, employing twists based on the Lie algebra Ξt of vector fields that are tangent to all the Mc. The twisted Cartan calculus is automatically equivariant under twisted Ξt. If we endow $\mathbb {R}^{n}$ ℝ n with a metric, then twisting and projecting to normal or tangent components commute, projecting the Levi-Civita connection to the twisted M is consistent, and in particular a twisted Gauss theorem holds, provided the twist is based on Killing vector fields. Twisted algebraic quadrics can be characterized in terms of generators and ⋆-polynomial relations. We explicitly work out deformations based on abelian or Jordanian twists of all quadrics in $\mathbb {R}^{3}$ ℝ 3 except ellipsoids, in particular twisted cylinders embedded in twisted Euclidean $\mathbb {R}^{3}$ ℝ 3 and twisted hyperboloids embedded in twisted Minkowski $\mathbb {R}^{3}$ ℝ 3 [the latter are twisted (anti-)de Sitter spaces dS2, AdS2].