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"Norman, Michael"
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Measuring the elastic modulus of soft culture surfaces and three-dimensional hydrogels using atomic force microscopy
Growing interest in exploring mechanically mediated biological phenomena has resulted in cell culture substrates and 3D matrices with variable stiffnesses becoming standard tools in biology labs. However, correlating stiffness with biological outcomes and comparing results between research groups is hampered by variability in the methods used to determine Young’s (elastic) modulus,
E
, and by the inaccessibility of relevant mechanical engineering protocols to most biology labs. Here, we describe a protocol for measuring
E
of soft 2D surfaces and 3D hydrogels using atomic force microscopy (AFM) force spectroscopy. We provide instructions for preparing hydrogels with and without encapsulated live cells, and provide a method for mounting samples within the AFM. We also provide details on how to calibrate the instrument, and give step-by-step instructions for collecting force-displacement curves in both manual and automatic modes (stiffness mapping). We then provide details on how to apply either the Hertz or the Oliver-Pharr model to calculate
E
, and give additional instructions to aid the user in plotting data distributions and carrying out statistical analyses. We also provide instructions for inferring differential matrix remodeling activity in hydrogels containing encapsulated single cells or organoids. Our protocol is suitable for probing a range of synthetic and naturally derived polymeric hydrogels such as polyethylene glycol, polyacrylamide, hyaluronic acid, collagen, or Matrigel. Although sample preparation timings will vary, a user with introductory training to AFM will be able to use this protocol to characterize the mechanical properties of two to six soft surfaces or 3D hydrogels in a single day.
This protocol describes how to use atomic force microscopy to measure the elastic modulus of soft 2D surfaces and cell-laden 3D hydrogels. We provide instructions for sample preparation, instrument calibration and data collection and analysis.
Journal Article
Norman Corwin's One world flight : the lost journal of radio's greatest writer
Chiefly the transcript of the CBS thirteen-part radio series, One world flight, that first aired in January,1947; provides a perspective of Corwin's travels to 37 countries in 1946, in the immediate post-World War era.
Book
The Challenge of Unconventional Superconductivity
During the past few decades, several new classes of superconductors have been discovered that do not appear to be related to traditional superconductors. The source of the superconductivity of these materials is likely different from the electron-ion interactions that are at the heart of conventional superconductivity. Developing a rigorous theory for any of these classes of materials has proven to be a difficult challenge and will remain one of the major problems in physics in the decades to come.
Journal Article
Norman Mailer : collected essays of the 1960s
\"This volume contains thirty-six essays published by Norman Mailer from November 1960 to September 1969, along with the preface to his 1963 collection The Presidential Papers and two prefaces he wrote for paperback editions of that book\"--(Note; page 471).
Book
ILC1 drive intestinal epithelial and matrix remodelling
Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6
+
epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial–mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.
Type-1 innate lymphoid cells have been shown to drive intestinal epithelial proliferation and extracellular matrix remodelling through TGF-β1 secretion, which could exacerbate inflammatory bowel disease comorbidities such as cancer and fibrosis.
Journal Article
Formation of massive black holes in rapidly growing pre-galactic gas clouds
The origin of the supermassive black holes that inhabit the centres of massive galaxies remains unclear
1
,
2
. Direct-collapse black holes—remnants of supermassive stars, with masses around 10,000 times that of the Sun—are ideal seed candidates
3
–
6
. However, their very existence and their formation environment in the early Universe are still under debate, and their supposed rarity makes modelling their formation difficult
7
,
8
. Models have shown that rapid collapse of pre-galactic gas (with a mass infall rate above some critical value) in metal-free haloes is a requirement for the formation of a protostellar core that will then form a supermassive star
9
,
10
. Here we report a radiation hydrodynamics simulation of early galaxy formation
11
,
12
that produces metal-free haloes massive enough and with sufficiently high mass infall rates to form supermassive stars. We find that pre-galactic haloes and their associated gas clouds that are exposed to a Lyman–Werner intensity roughly three times the intensity of the background radiation and that undergo at least one period of rapid mass growth early in their evolution are ideal environments for the formation of supermassive stars. The rapid growth induces substantial dynamical heating
13
,
14
, amplifying the Lyman–Werner suppression that originates from a group of young galaxies 20 kiloparsecs away. Our results strongly indicate that the dynamics of structure formation, rather than a critical Lyman–Werner flux, is the main driver of the formation of massive black holes in the early Universe. We find that the seeds of massive black holes may be much more common than previously considered in overdense regions of the early Universe, with a co-moving number density up to 10
−3
per cubic megaparsec.
Simulations of early galaxy formation suggest that the dynamics of structure formation, rather than the Lyman–Werner flux, drives the formation of massive black holes in the early Universe.
Journal Article
Many-Body Electronic Structure of NdNiO2 and CaCuO2
The demonstration of superconductivity in nickelate analogs of highTccuprates provides new perspectives on the physics of correlated electron materials. The degree to which the nickelate electronic structure is similar to that of cuprates is an important open question. This paper presents results of a comparative study of the many-body electronic structure and theoretical phase diagram of the isostructural materialsCaCuO2andNdNiO2. BothNdNiO2andCaCuO2are found to be charge transfer materials. Important differences include the proximity of the oxygen2pbands to the Fermi level, the bandwidth of the transition metal-derived3dbands, and the presence, inNdNiO2, of both Nd-derived5dstates crossing the Fermi level and a van Hove singularity that crosses the Fermi level as the out-of-plane momentum is varied. The low-energy physics ofNdNiO2is found to be that of a single Ni-derived correlated band, with additional accompanying weakly correlated bands of Nd-derived states that dope the Ni-derived band. The effective correlation strength of the Ni-deriveddband crossing the Fermi level inNdNiO2is found to be greater than that of the Cu-deriveddband inCaCuO2, but the predicted magnetic transition temperature ofNdNiO2is substantially lower than that ofCaCuO2because of the smaller bandwidth.
Journal Article