Bistability of cell-matrix adhesions resulting from non-linear receptor-ligand dynamics

Bistability is a major mechanism for cellular decision making and usually results from positive feedback in biochemical control systems. Here we show theoretically that bistability between unbound and bound states of adhesion clusters results from positive feedback mediated by structural rather than biochemical processes, namely by receptor-ligand dissociation and association dynamics which depend non-linearly on mechanical force and receptor-ligand separation. For small cell-matrix adhesions, we find rapid switching between unbound and bound states, which in the initial stages of adhesion allows the cell to explore its environment through many transient adhesions.Comment: Revtex, 3 pages, 3 postscript figures included, to appear in Biophysical Journal as Biophysical Lette

Focal adhesions as mechanosensors: the two-spring model

Adhesion-dependent cells actively sense the mechanical properties of their environment through mechanotransductory processes at focal adhesions, which are integrin-based contacts connecting the extracellular matrix to the cytoskeleton. Here we present first steps towards a quantitative understanding of focal adhesions as mechanosensors. It has been shown experimentally that high levels of force are related to growth of and signaling at focal adhesions. In particular, activation of the small GTPase Rho through focal adhesions leads to the formation of stress fibers. Here we discuss one way in which force might regulate the internal state of focal adhesions, namely by modulating the internal rupture dynamics of focal adhesions. A simple two-spring model shows that the stiffer the environment, the more efficient cellular force is built up at focal adhesions by molecular motors interacting with the actin filaments.Comment: Latex, 17 pages, 5 postscript figures include

The role of spatial averaging in the precision of gene expression patterns

During embryonic development, differentiating cells respond via gene expression to positional cues from morphogen gradients. While gene expression is often highly erratic, embryonic development is precise. We show by theory and simulations that diffusion of the expressed protein can enhance the precision of its expression domain. While diffusion lessens the sharpness of the expression boundary, it also reduces super-Poissonian noise by washing out bursts of gene expression. Balancing these effects yields an optimal diffusion constant maximizing the precision of the expression domain.Comment: 5 pages, 4 EPS figure

Focal adhesions as mechanosensors: the two-spring model

Adhesion-dependent cells actively sense the mechanical properties of their environment through mechanotransductory processes at focal adhesions, which are integrin-based contacts connecting the extracellular matrix to the cytoskeleton. Here we present first steps towards a quantitative understanding of focal adhesions as mechanosensors. It has been shown experimentally that high levels of force are related to growth of and signaling at focal adhesions. In particular, activation of the small GTPase Rho through focal adhesions leads to the formation of stress fibers. Here we discuss one way in which force might regulate the internal state of focal adhesions, namely by modulating the internal rupture dynamics of focal adhesions. A simple two-spring model shows that the stiffer the environment, the more efficient cellular force is built up at focal adhesions by molecular motors interacting with the actin filaments.Comment: Latex, 17 pages, 5 postscript figures include

Überlagerung von sozialer und ethnischer Segregation in Hamburg

Der Beitrag analysiert die kleinräumige Verteilung der Hamburger Bevölkerung im Hinblick auf ihren sozialen Status ihre ethnische Zugehörigkeit auf der Basis von Daten aus der Bevölkerungs- und Sozialhilfestatistik. Die Stadtteile mit einem hohen Armenanteil unter der deutschen Bevölkerung befinden sich hauptsächlich in Hafen-Innenstadtnähe sowie in den durch sozialen Mietwohnungsbau geprägten Gegenden am Stadtrand. Es handelt sich dabei oftmals um die klassischen Arbeiterwohngebiete, die durch ein ungünstiges Wohnumfeld sowie einen unterdurchschnittlichen Bildungsstand und vergleichsweise geringe Einkommen der Bewohner gekennzeichnet sind. Die Armutshochburgen der ausländischen Bevölkerung sind dagegen ungleichmäßiger im Stadtgebiet verteilt. Besonders in einigen siedlungsstrukturell unauffälligen Vierteln am Stadtrand, in denen zahlreiche Asylbewerber untergebracht sind, erreichen die Armutsquoten der Nichtdeutschen überdurchschnittliche Werte. In den traditionellen Ausländerwohnquartieren in Hafennähe sind dagegen nichtdeutsche Personen kaum häufiger von Armut betroffen als in der Gesamtstadt. Die stadtteilbezogenen Unterschiede in Bezug auf die Armutsquote der Deutschen waren im Zeitverlauf weitgehend stabil, wogegen sich bei den Ausländern infolge ihrer höheren Mobilität größere Veränderungen ergeben hatten. Beim Vergleich der regionalen Verteilung der einzelnen nach Sozialstatus und ethnischer Zugehörigkeit abgegrenzten Bevölkerungsgruppen zeigt sich für arme Deutsche und arme Ausländer die größte räumliche Nähe. Auch bei armen Deutschen und wohlhabenden Ausländern besteht noch eine vergleichsweise große Übereinstimmung der Wohnorte. Dagegen weisen wohlhabende Deutsche eine deutlich größere räumliche Distanz sowohl zu armen als auch zu wohlhabenden Ausländern auf. Dies gilt auffälligerweise auch für das Verhältnis zwischen wohlhabenden und armen Ausländern. Im Zeitverlauf sind wohlhabende Deutsche und wohlhabende Ausländer etwas stärker zusammengerückt, was als zunehmende gesellschaftliche Integration von Ausländern gedeutet werden kann. Auf der anderen Seite lässt sich aber innerhalb der nichtdeutschen Einwohnerschaft eine deutliche räumliche Entmischung zwischen wohlhabenden und armen Bevölkerungsteilen erkennen. Obwohl Ausländer in nahezu allen Stadtteilen deutlich häufiger von Einkommensarmut betroffen sind als deutsche Einwohner, war die wechselseitige Beeinflussung zwischen der sozialen und der ethnischen Segregation nur gering. Die regionale Ungleichverteilung von Deutschen und Ausländern kann nicht als Folge der sozialen Segregation gedeutet werden.This article analyses the distribution of Hamburg's population in a small space with a view towards its social status and ethnic affiliation based upon data from the population and social welfare statistics. The boroughs with a large proportion of poor persons among the German population are mainly in the area of the port and city centre and on the outskirts of the city with rented social housing. These are often the classical workers' quarters and their main features are an unfavourable housing environment, below-average education and comparably low incomes among the inhabitants. In contrast, the strongholds of poverty of the foreign population are distributed more unevenly in the urban area. The poverty rates among the non-German population reach above-average values especially in some quarters on the outskirts of the city with an unobtrusive settlement structure where many asylum seekers are housed. In contrast, non-German persons are hardly affected more frequently by poverty in the traditional foreigners' quarters in the area of the port than in the city as a whole. The differences with reference to the poverty rate of Germans based upon boroughs remained stable to a great extent in the course of time. But in contrast, there were greater differences among foreigners because of their greater mobility. When comparing the regional distribution of the individual population groups delineated according to social status and ethnic affiliation, we can see that poor Germans and poor foreigners are very close to one another. But the residential locations of poor Germans and prosperous foreigners coincide to a great extent. In contrast, prosperous Germans have a significantly greater distance both to poor and prosperous foreigners. This also noticeably applies to the relationship between prosperous and poor foreigners. Prosperous Germans and foreigners have come closer together in the course of time, which we may interpret as increasing social integration of foreigners. On the other hand, we can see a clear spatial demixing among prosperous and poor population segments within the group of non-German inhabitants. Although foreigners are clearly more frequently affected by income poverty in almost all boroughs than the German inhabitants, the alternating influence between social and ethnic segregation was only slight. The unequal distribution of Germans and foreigners in the region cannot be interpreted as a consequence of social segregation