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

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 Right to Work and Finding Work: the Inaccessibility of Private and Public Sector Career Portals

The right to participation in society for people with disabilities is relatively well established in national and international law and convention (UNCRPD), and increasingly in social norms. These rights include the right to work. The majority of job opportunities today are advertised and applied for almost exclusively online in digital form. In late 2017 we performed both automated testing of career sites against WCAG 2.0 and BITV standards and a multi-day detailed laboratory observation of visually impaired and blind testers applying for jobs across 10 German organisations in the public and private sectors. The tests note significant problems with the accessibility of the career sites, both in terms of standards compliance and practical use testing. This study illustrates the barriers that digital technologies can create for people with disabilities. This paper will highlight and classify these issues, explore their causes, and briefly suggest improvements for software developers, employers and regulators

Generation of an Advanced Helicopter Experimental Aerodynamic Database for CFD Code Validation (GOAHEAD)

During the last ten years considerable progress has been made in the development of aerodynamic prediction capabilities by means of CFD for isolated helicopter components such as an isolated main rotor or an isolated fuselage. Today leading edge CFD software systems are available which are capable of predicting the viscous flow around complete helicopters. The greatest shortcoming in Europe for qualifying RANS methods as design tools in the industrial design process for helicopters is the lack of detailed experimental validation data for the aerodynamics of complete helicopters. This issue was addressed by the European GOAHEAD research project (Generation of Advanced Helicopter Experimental Aerodynamic Database for CFD code validation). The presentation will give an overview over the results obtained in GOAHEAD: Within the project a wind tunnel experiment for a complete helicopter configuration consisting of fuselage, main and tail rotor was conducted. The wind tunnel set-up, the extensive model instrumentation and the wind tunnel test matrix were chosen to satisfy the requirements for validation of CFD methods. Results of the campaign in the DNW-LLF wind tunnel include unsteady pressures and loads, laminar/turbulent transition lines, blade deformation data and flow field visualization by means of PIV. The data were analysed in detail and a comprehensive documentation was generated for the experimental data base. In parallel to the wind tunnel experiment six European CFD codes were applied by 11 partners from industry, research organizations and universities in a blind test and post test exercise. The comparison of the computational results provides an assessment of different code features, allows to evaluate the reliability of the codes and gives directions for further code developments. The progress made within GOAHEAD is a big step forward having in mind that the first successful RANS helicopter simulations in Europe have been published in 2002

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