Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair

Eukaryotic cells possess a universal repair machinery that ensures rapid resealing of plasma membrane disruptions. Before resealing, the torn membrane is submitted to considerable tension, which functions to expand the disruption. Here we show that annexin-A5 (AnxA5), a protein that self-assembles into two-dimensional (2D) arrays on membranes upon Ca2+ activation, promotes membrane repair. Compared with wild-type mouse perivascular cells, AnxA5-null cells exhibit a severe membrane repair defect. Membrane repair in AnxA5-null cells is rescued by addition of AnxA5, which binds exclusively to disrupted membrane areas. In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair. We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca2+, AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing

Generalized Toda Theory from Six Dimensions and the Conifold

Recently, a physical derivation of the Alday-Gaiotto-Tachikawa correspondence has been put forward. A crucial role is played by the complex Chern-Simons theory arising in the 3d-3d correspondence, whose boundary modes lead to Toda theory on a Riemann surface. We explore several features of this derivation and subsequently argue that it can be extended to a generalization of the AGT correspondence. The latter involves codimension two defects in six dimensions that wrap the Riemann surface. We use a purely geometrical description of these defects and find that the generalized AGT setup can be modeled in a pole region using generalized conifolds. Furthermore, we argue that the ordinary conifold clarifies several features of the derivation of the original AGT correspondence.Comment: 27+2 pages, 3 figure

Standard of hygiene and immune adaptation in newborn infants

Peer reviewe

High-speed AFM height spectroscopy reveals µs-dynamics of unlabeled biomolecules

Dynamics are fundamental to the functions of biomolecules and can occur on a wide range of time and length scales. Here we develop and apply high-speed AFM height spectroscopy (HS-AFM-HS), a technique whereby we monitor the sensing of a HS-AFM tip at a fixed position to directly detect the motions of unlabeled molecules underneath. This gives Angstrom spatial and microsecond temporal resolutions. In conjunction with HS-AFM imaging modes to precisely locate areas of interest, HS-AFM-HS measures simultaneously surface concentrations, diffusion coefficients and oligomer sizes of annexin-V on model membranes to decipher key kinetics allowing us to describe the entire annexin-V membrane-association and self-assembly process in great detail and quantitatively. This work displays how HS-AFM-HS can assess the dynamics of unlabeled bio-molecules over several orders of magnitude and separate the various dynamic components spatiotemporally