A Multiwell Platform for Studying Stiffness-Dependent Cell Biology

Adherent cells are typically cultured on rigid substrates that are orders of magnitude stiffer than their tissue of origin. Here, we describe a method to rapidly fabricate 96 and 384 well platforms for routine screening of cells in tissue-relevant stiffness contexts. Briefly, polyacrylamide (PA) hydrogels are cast in glass-bottom plates, functionalized with collagen, and sterilized for cell culture. The Young's modulus of each substrate can be specified from 0.3 to 55 kPa, with collagen surface density held constant over the stiffness range. Using automated fluorescence microscopy, we captured the morphological variations of 7 cell types cultured across a physiological range of stiffness within a 384 well plate. We performed assays of cell number, proliferation, and apoptosis in 96 wells and resolved distinct profiles of cell growth as a function of stiffness among primary and immortalized cell lines. We found that the stiffness-dependent growth of normal human lung fibroblasts is largely invariant with collagen density, and that differences in their accumulation are amplified by increasing serum concentration. Further, we performed a screen of 18 bioactive small molecules and identified compounds with enhanced or reduced effects on soft versus rigid substrates, including blebbistatin, which abolished the suppression of lung fibroblast growth at 1 kPa. The ability to deploy PA gels in multiwell plates for high throughput analysis of cells in tissue-relevant environments opens new opportunities for the discovery of cellular responses that operate in specific stiffness regimes

Joint analysis of Dark Energy Survey Year 3 data and CMB lensing from SPT and Planck. II. Cross-correlation measurements and cosmological constraints

Cross-correlations of galaxy positions and galaxy shears with maps of gravitational lensing of the cosmic microwave background (CMB) are sensitive to the distribution of large-scale structure in the Universe. Such cross-correlations are also expected to be immune to some of the systematic effects that complicate correlation measurements internal to galaxy surveys. We present measurements and modeling of the cross-correlations between galaxy positions and galaxy lensing measured in the first three years of data from the Dark Energy Survey with CMB lensing maps derived from a combination of data from the 2500 deg2 SPT-SZ survey conducted with the South Pole Telescope and full-sky data from the Planck satellite. The CMB lensing maps used in this analysis have been constructed in a way that minimizes biases from the thermal Sunyaev Zel'dovich effect, making them well suited for cross-correlation studies. The total signal-to-noise of the cross-correlation measurements is 23.9 (25.7) when using a choice of angular scales optimized for a linear (nonlinear) galaxy bias model. We use the cross-correlation measurements to obtain constraints on cosmological parameters. For our fiducial galaxy sample, which consist of four bins of magnitude-selected galaxies, we find constraints of ωm=0.272-0.052+0.032 and S8σ8ωm/0.3=0.736-0.028+0.032 (ωm=0.245-0.044+0.026 and S8=0.734-0.028+0.035) when assuming linear (nonlinear) galaxy bias in our modeling. Considering only the cross-correlation of galaxy shear with CMB lensing, we find ωm=0.270-0.061+0.043 and S8=0.740-0.029+0.034. Our constraints on S8 are consistent with recent cosmic shear measurements, but lower than the values preferred by primary CMB measurements from Planck

Joint analysis of Dark Energy Survey Year 3 data and CMB lensing from SPT and Planck. I. Construction of CMB lensing maps and modeling choices

Joint analyses of cross-correlations between measurements of galaxy positions, galaxy lensing, and lensing of the cosmic microwave background (CMB) offer powerful constraints on the large-scale structure of the Universe. In a forthcoming analysis, we will present cosmological constraints from the analysis of such cross-correlations measured using Year 3 data from the Dark Energy Survey (DES), and CMB data from the South Pole Telescope (SPT) and Planck. Here we present two key ingredients of this analysis: (1) an improved CMB lensing map in the SPT-SZ survey footprint and (2) the analysis methodology that will be used to extract cosmological information from the cross-correlation measurements. Relative to previous lensing maps made from the same CMB observations, we have implemented techniques to remove contamination from the thermal Sunyaev Zel'dovich effect, enabling the extraction of cosmological information from smaller angular scales of the cross-correlation measurements than in previous analyses with DES Year 1 data. We describe our model for the cross-correlations between these maps and DES data, and validate our modeling choices to demonstrate the robustness of our analysis. We then forecast the expected cosmological constraints from the galaxy survey-CMB lensing auto and cross-correlations. We find that the galaxy-CMB lensing and galaxy shear-CMB lensing correlations will on their own provide a constraint on S8=σ8ωm/0.3 at the few percent level, providing a powerful consistency check for the DES-only constraints. We explore scenarios where external priors on shear calibration are removed, finding that the joint analysis of CMB lensing cross-correlations can provide constraints on the shear calibration amplitude at the 5% to 10% level

Dark Energy Survey Year 1 Results:Methodology and Projections for Joint Analysis of Galaxy Clustering, Galaxy Lensing, and CMB Lensing Two-point Functions

Optical imaging surveys measure both the galaxy density and the gravitational lensing-induced shear fields across the sky. Recently, the Dark Energy Survey (DES) collaboration used a joint fit to two-point correlations between these observables to place tight constraints on cosmology (DES Collaboration et al. 2017). In this work, we develop the methodology to extend the DES year one joint probes analysis to include cross-correlations of the optical survey observables with gravitational lensing of the cosmic microwave background (CMB) as measured by the South Pole Telescope (SPT) and Planck. Using simulated analyses, we show how the resulting set of five two-point functions increases the robustness of the cosmological constraints to systematic errors in galaxy lensing shear calibration. Additionally, we show that contamination of the SPT+Planck CMB lensing map by the thermal Sunyaev-Zel'dovich effect is a potentially large source of systematic error for two-point function analyses, but show that it can be reduced to acceptable levels in our analysis by masking clusters of galaxies and imposing angular scale cuts on the two-point functions. The methodology developed here will be applied to the analysis of data from the DES, the SPT, and Planck in a companion work.Comment: 21 pages, 11 figures; matches version resubmitted to journa

Dark Energy Survey Year 1 Results:tomographic cross-correlations between DES galaxies and CMB lensing from SPT+Planck

International audienceWe measure the cross-correlation between redMaGiC galaxies selected from the Dark Energy Survey (DES) year 1 data and gravitational lensing of the cosmic microwave background (CMB) reconstructed from South Pole Telescope (SPT) and Planck data over 1289  deg2. When combining measurements across multiple galaxy redshift bins spanning the redshift range of 0.15<z<0.90, we reject the hypothesis of no correlation at 19.9σ significance. When removing small-scale data points where thermal Sunyaev-Zel’dovich signal and nonlinear galaxy bias could potentially bias our results, the detection significance is reduced to 9.9σ. We perform a joint analysis of galaxy-CMB lensing cross-correlations and galaxy clustering to constrain cosmology, finding Ωm=0.276-0.030+0.029 and S8=σ8Ωm/0.3=0.800-0.094+0.090. We also perform two alternate analyses aimed at constraining only the growth rate of cosmic structure as a function of redshift, finding consistency with predictions from the concordance ΛCDM model. The measurements presented here are part of a joint cosmological analysis that combines galaxy clustering, galaxy lensing and CMB lensing using data from DES, SPT and Planck