Fluctuation assisted spreading of a fluid filled elastic blister

In this theoretical and numerical study, we show how spatially extended fluctuations can influence and dominate the dynamics of a fluid filled elastic blister as is deforms onto a pre-wetted solid substrate. To describe the blister dynamics, we develop a stochastic elastohydrodynamic framework that couples the viscous flow, the elastic bending of the interface and the noise from the environment. We deploy a scaling analysis to find the elastohydrodynamic spreading law $\hat R\sim {\hat t}^{1/11}$ a direct analogue to the capillary spreading of drops, while the inclusion of noise in our model highlights that the dynamics speed-up significantly $\hat R\sim {\hat t}^{1/6}$ as local changes in curvature enhance the peeling of the elastic interface from the substrate. Moreover, our analysis identifies a distinct criterion for the transition between the deterministic and stochastic spreading regime, which is further illustrated by numerical simulations

Agentenbasierte Modellierung der Dynamik immunologischer Synapsen

Adaptive immune responses require the exchange of information between T cells and Antigen Presenting cells (APCs). T cell receptors (TCRs) search and bind to processed antigen peptide bound to major histocompatibility complexes (pMHC) on the APC surface. During this process the surface molecules of the two cells are re-organized into a characteristic spatial pattern, known as Immunological Synapse (IS). The contact interface is segregated in three distinct regions, the central, peripheral and distal supramolecular activation clusters (c, p and dSMAC), occupied by different molecules. The formation of a stable IS leads to key events during the immune response, including T cell activation, fate decision and effector function such as killing of infected cells. An agent-based model based on TCR-pMHC and LFA-1-ICAM-1 interactions was developed in order to investigate the mechanisms leading to the characteristic IS formation. Size-based segregation (SBS) for different sized complexes and coupling of molecules to the centripetal flow of F-actin are the considered mechanisms, and are discussed for additional molecules, such as the costimulatory CD28 and CD2, as well as the CD45 phosphatase, all important for TCR signaling. SBS and centripetal flow resulted in the accumulation of TCR-pMHC in the center of the IS and the emergence of a peripheral LFA-1-ICAM-1 gradient which acted as an exclusion mechanism of molecules and complexes from the IS. The model predicted a mechanism of CD28/CD2 movement, according to which CD28/CD2 complexes passively follow TCR-pMHC movement. The characteristic annular CD28-CD80 pattern around the cSMAC only emerged with a particular CD28-actin coupling strength that induced a centripetal motion, whereas the CD2 corolla pattern formation required a CD2-CD2 self attraction but no interaction with the actin network. The centripetal flow of TCR-pMHC complexes acted as a mechanism of TCR cooperativity, while active modulation of the association rate by F-actin foci showed that the global affinity of TCR toward pMHC molecules can be positively modulated. The efforts to understand the mechanisms of IS formation can help in developing therapeutic targets aiming the formation of stable synapses, in cases like cancer and autoimmune diseases where impaired and unstable synapses and therefore defects on T cell activation are observed.Adaptive Immunreaktionen erfordern den Informationsaustausch zwischen T-Zellen und Antigen Presenting-Zellen (APCs). T-Zell-Rezeptoren (TCR) suchen und binden an prozessierte Antigenpeptide, die auf pMHC auf der APC-Oberfläche gebunden sind. Während dieses Vorgangs werden die Oberflaechenmoleküle der beiden Zellen zu einem charakteristischen räumlichen Muster reorganisiert, das als Immunologische Synapse (IS) bekannt ist. Die IS ist in drei verschiedene Bereiche unterteilt, die zentralen, peripheren und distalen supramolekularen Aktivierungscluster (c, p und dSMAC), die von verschiedenen Molekülen besetzt sind. Die Bildung einer stabilen IS führt zu Schlüsselereignissen während der Immunreaktion, wie der T-Zell-Aktivierung oder Differenzierung zu Subtypen wie der zytotoxischen T-Zelle. Ein Agenten-basiertes Modell wurde entwickelt, das TCR-pMHC und LFA-1-ICAM-1 Wechselwirkungen beschreibt, um die Mechanismen der Bildung von IS zu untersuchen. Die größenbasierte Segregation (SBS) für unterschiedliche große Komplexe und die Ankopplung von Molekülen an den zentripetalen Fluss von F-Aktin wurden implementiert und für die TCR-Signalvermittlung wichtigen kostimulatorischen Moleküle CD28 und CD2 sowie die CD45-Phosphatase diskutiert. SBS und F-Aktin Zentripetalfluss führten zur Ansammlung von TCR-pMHC im Zentrum der IS und zur Entstehung eines peripheren LFA-1-ICAM-1-Gradienten, der als Ausschlussmechanismus von Molekülen und Komplexen aus der IS fungierte. Das Modell sagte einen neuen Mechanismus vorher, nach dem CD28/CD2 den TCR-pMHC-Komplexen passiv in Microclustern folgen. Das ringförmige CD28-CD80-Muster um den cSMAC erfordert deren zentrale Bewegung mit einer bestimmten CD28-Aktin-Kopplungsstärke. Die CD2 corolla-Bildung erfordert eine CD2-CD2-Selbstanziehung aber keine Kopplung an F-Aktin. Der Zentripetalfluss von TCR-pMHC-Komplexen wirkte als Mechanismus der TCR Kooperativität. Die aktive Modulation der Assoziationsrate durch F-Aktin-Foci ermöglicht eine Modulation der globale Affinität von TCR und pMHC-Molekülen. Das verbesserte Verständnis der Mechanismen der IS-Bildung kann helfen, Therapien zu entwickeln, die auf die Bildung stabiler Synapsen abzielen, beispielsweise bei Krebs und Autoimmunerkrankungen, bei denen beeinträchtigte und instabile Synapsen und daher Defekte bei der T-Zellaktivierung beobachtet werden

The irreversible thermodynamics of curved lipid membranes

The theory of irreversible thermodynamics for arbitrarily curved lipid membranes is presented here. The coupling between elastic bending and irreversible processes such as intra-membrane lipid flow, intra-membrane phase transitions, and protein binding and diffusion is studied. The forms of the entropy production for the irreversible processes are obtained, and the corresponding thermodynamic forces and fluxes are identified. Employing the linear irreversible thermodynamic framework, the governing equations of motion along with appropriate boundary conditions are provided.Comment: 62 pages, 4 figure

Elastohydrodynamics and Kinetics of Protein Patterning in the Immunological Synapse

We propose a minimal mathematical model for the physical basis of membrane protein patterning in the immunological synapse (IS), which encompass membrane mechanics, protein binding kinetics and motion, and fluid flow in the synaptic cleft. Our theory leads to simple predictions for the spatial and temporal scales of protein cluster formation, growth and arrest as a function of membrane stiffness, rigidity and kinetics of the adhesive proteins, and the fluid flow in the synaptic cleft. Numerical simulations complement these scaling laws by quantifying the nucleation, growth and stabilization of proteins domains on the size of the cell. Direct comparison with experiment shows that passive elastohydrodynamics and kinetics of protein binding in the synaptic cleft can describe the short-time formation and organization of protein clusters, without evoking any active processes in the cytoskeleton. Despite the apparent complexity of the process, our analysis shows that just two dimensionless parameters characterize the spatial and temporal evolution of the protein pattern: a ratio of membrane elasticity to protein stiffness, and the ratio of a hydrodynamic time scale for fluid flow relative to the protein binding rate. A simple phase diagram encompasses the variety of patterns that can arise