Dataset Information

Cellular tension encodes local Src-dependent differential ?₁ and ?₃ integrin mobility.

ABSTRACT: Integrins are transmembrane receptors that have a pivotal role in mechanotransduction processes by connecting the extracellular matrix to the cytoskeleton. Although it is well established that integrin activation/inhibition cycles are due to highly dynamic interactions, whether integrin mobility depends on local tension and cytoskeletal organization remains surprisingly unclear. Using an original approach combining micropatterning on glass substrates to induce standardized local mechanical constraints within a single cell with temporal image correlation spectroscopy, we measured the mechanosensitive response of integrin mobility at the whole cell level and in adhesion sites under different mechanical constraints. Contrary to ?1 integrins, high tension increases ?3 integrin residence time in adhesive regions. Chimeric integrins and structure-function studies revealed that the ability of ?3 integrins to specifically sense local tensional organization is mostly encoded by its cytoplasmic domain and is regulated by tuning the affinity of its NPXY domains through phosphorylation by Src family kinases.

SUBMITTER: De Mets R

PROVIDER: S-EPMC6589565 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Cellular tension encodes local Src-dependent differential β<sub>1</sub> and β<sub>3</sub> integrin mobility.

De Mets Richard R Wang Irene I Balland Martial M Oddou Christiane C Moreau Philippe P Fourcade Bertrand B Albiges-Rizo Corinne C Delon Antoine A Destaing Olivier O

Molecular biology of the cell 20181121 2

Integrins are transmembrane receptors that have a pivotal role in mechanotransduction processes by connecting the extracellular matrix to the cytoskeleton. Although it is well established that integrin activation/inhibition cycles are due to highly dynamic interactions, whether integrin mobility depends on local tension and cytoskeletal organization remains surprisingly unclear. Using an original approach combining micropatterning on glass substrates to induce standardized local mechanical const ...[more]

PMID: 30462575

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Project description:Infectious disease transmission is an inherently spatial process in which a host's home location and their social mixing patterns are important, with the mixing of infectious individuals often different to that of susceptible individuals. Although incidence data for humans have traditionally been aggregated into low-resolution data sets, modern representative surveillance systems such as electronic hospital records generate high volume case data with precise home locations. Here, we use a gridded spatial transmission model of arbitrary resolution to investigate the theoretical relationship between population density, differential population movement and local variability in incidence. We show analytically that a uniform local attack rate is typically only possible for individual pixels in the grid if susceptible and infectious individuals move in the same way. Using a population in Guangdong, China, for which a robust quantitative description of movement is available (a travel kernel), and a natural history consistent with pandemic influenza; we show that local cumulative incidence is positively correlated with population density when susceptible individuals are more connected in space than infectious individuals. Conversely, under the less intuitively likely scenario, when infectious individuals are more connected, local cumulative incidence is negatively correlated with population density. The strength and direction of correlation changes sign for other kernel parameter values. We show that simulation models in which it is assumed implicitly that only infectious individuals move are assuming a slightly unusual specific correlation between population density and attack rate. However, we also show that this potential structural bias can be corrected by using the appropriate non-isotropic kernel that maps infectious-only code onto the isotropic dual-mobility kernel. These results describe a precise relationship between the spatio-social mixing of infectious and susceptible individuals and local variability in attack rates. More generally, these results suggest a genuine risk that mechanistic models of high-resolution attack rate data may reach spurious conclusions if the precise implications of spatial force-of-infection assumptions are not first fully characterized, prior to models being fit to data.

Dataset Information

Cellular tension encodes local Src-dependent differential ?1 and ?3 integrin mobility.

Publications

Cellular tension encodes local Src-dependent differential β<sub>1</sub> and β<sub>3</sub> integrin mobility.

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Cellular tension encodes local Src-dependent differential ?₁ and ?₃ integrin mobility.