Inherent Interfacial Mechanical Gradients in 3D Hydrogels Influence Tumor Cell Behaviors

Cells sense and respond to the rigidity of their microenvironment by altering their morphology and migration behavior. To examine this response, hydrogels with a range of moduli or mechanical gradients have been developed. Here, we show that edge effects inherent in hydrogels supported on rigid substrates also influence cell behavior. A Matrigel hydrogel was supported on a rigid glass substrate, an interface which computational techniques revealed to yield relative stiffening close to the rigid substrate support. To explore the influence of these gradients in 3D, hydrogels of varying Matrigel content were synthesized and the morphology, spreading, actin organization, and migration of glioblastoma multiforme (GBM) tumor cells were examined at the lowest (<50 µm) and highest (>500 µm) gel positions. GBMs adopted bipolar morphologies, displayed actin stress fiber formation, and evidenced fast, mesenchymal migration close to the substrate, whereas away from the interface, they adopted more rounded or ellipsoid morphologies, displayed poor actin architecture, and evidenced slow migration with some amoeboid characteristics. Mechanical gradients produced via edge effects could be observed with other hydrogels and substrates and permit observation of responses to multiple mechanical environments in a single hydrogel. Thus, hydrogel-support edge effects could be used to explore mechanosensitivity in a single 3D hydrogel system and should be considered in 3D hydrogel cell culture systems

On the characterization of the heterogeneous mechanical response of human brain tissue

The mechanical characterization of brain tissue is a complex task that scientists have tried to accomplish for over 50 years. The results in the literature often differ by orders of magnitude because of the lack of a standard testing protocol. Different testing conditions (including humidity, temperature, strain rate), the methodology adopted, and the variety of the species analysed are all potential sources of discrepancies in the measurements. In this work, we present a rigorous experimental investigation on the mechanical properties of human brain, covering both grey and white matter. The influence of testing conditions is also shown and thoroughly discussed. The material characterization performed is finally adopted to provide inputs to a mathematical formulation suitable for numerical simulations of brain deformation during surgical procedures.</p

Mechanics of amorphous solids-identification and constitutive modelling

Both polymers and metals can be in an organised crystalline or amorphous glassy state, where for polymers usually at least a part of the structure is amorphous and metals are in a glassy state only when processed under special conditions. At the 15th European Mechanics of Materials Conference in September 2016 in Brussels, Belgium, a session focussing on the mechanical properties of amorphous or partly amorphous solid materials was organised, attempting to bridge descriptions found for metallic glasses and polymers, which share some common features, such as a rate- and temperature-dependent response, being prone to strain localisation in the form of shear bands, the occurrence of damage by cavitation, etc

Climb-enabled discrete dislocation plasticity

A small strain two-dimensional discrete dislocation plasticity framework coupled to vacancy diffusion is developed wherein the motion of edge dislocations is by a combination of glide and climb. The dislocations are modelled as line defects in a linear elastic medium and the mechanical boundary value problem is solved by the superposition of the infinite medium elastic fields of the dislocations and a complimentary non-singular solution that enforces the boundary conditions. Similarly, the climbing dislocations are modelled as line sources/sinks of vacancies and the vacancy diffusion boundary value problem is also solved by a superposition of the fields of the line sources/sinks in an infinite medium and a complementary non-singular solution that enforces the boundary conditions. The vacancy concentration field along with the stress field provides the climb rate of the dislocations. Other short-range interactions of the dislocations are incorporated via a set of constitutive rules. We first employ this formulation to investigate the climb of a single edge dislocation in an infinite medium and illustrate the existence of diffusion-limited and sink-limited climb regimes. Next, results are presented for the pure bending and uniaxial tension of single crystals oriented for single slip. These calculations show that plasticity size effects are reduced when dislocation climb is permitted. Finally, we contrast predictions of this coupled framework with an ad hoc model in which dislocation climb is modelled by a drag-type relation based on a quasi steady-state solution. © 2013 Elsevier Ltd. All rights reserved

Multi-scale microstructure evolution of tungsten under neutron and plasma loads

Tungsten (W) owing to its excellent high temperature properties, is the candidate material for plasma facing components in fusion reactors such as ITER and DEMO. However, the lifetime of the tungsten based plasma facing component and thereby the lifetime of the reactor, is dictated by the extreme particle (neutron and ions) and heat loads, and is not very well understood. The fast neutrons result in the generation of point and clustered lattice defects, which further interact with the plasma based helium ions, leading to nucleation and growth of helium bubbles. Additionally, these interactions in combination with high temperatures influence the microstructural evolutionby grain growth and recrystallization process, ultimately affecting the mechanical and thermal properties. Thus, an in-depth understanding on the role of helium ions in conjunction with heat and neutron loads is crucial for predicting the microstructure evolution under fusion conditions accurately.In the present work, a multi-scale model describing the simultaneous effect of the defect generation by neutron irradiation and helium implantation from the plasma, considering irradiation time scales of hours and component length scales is developed. At atomic length scales, the generation of defects such as the vacancies, self-interstitial atoms, their clustering and the trapping of helium at defects and their clusters are modelledusing a kinetic rate theory approach. Additionally, these microstructurallevel interactions are linked to mesoscopic length scales by considering the diffusion of mobile defects along the tungsten monoblock depth (ITER specifications). The spatially varying defect concentrations from the model are also used to obtain a measure of the spatially varying lattice stored energy, thereby allowing to link the effect of helium with mechanisms such as recrystallization and grain growth. The influence of the helium resolution from existing bubbles and microstructural sinks on the helium diffusionlength scales is investigated. Furthermore, the effect of helium cluster mobility on the overall helium retention in tungsten is found to be less-pronounced

Controlled irradiation hardening of tungsten by cyclic recrystallization

\u3cp\u3eThe economical lifetime of the divertor is a key concern for realizing nuclear fusion reactors that may solve the world's energy problem. A main risk is thermo-mechanical failure of the plasma-facing tungsten monoblocks, as a consequence of irradiation hardening induced by neutron displacement cascades. Lifetime extensions that could be carried out without prolonged maintenance periods are desired. In this work, the effects of potential treatments for extending the lifetime of an operational reactor are explored. The proposed treatments make use of cyclic recrystallization processes that can occur in neutron-irradiated tungsten. Evolution of the microstructure under non-isothermal conditions is investigated, employing a multi-scale model that includes a physically-based mean-field recrystallization model and a cluster dynamics model for neutron irradiation effects. The model takes into account microstructural properties such as grain size and displacement-induced defect concentrations. The evolution of a hardness indicator under neutron irradiation was studied. The results reveal that, for the given microstructure and under the assumed model behaviour, periodical extra heating can have a significant positive influence on controlling the irradiation hardening. For example, at 800 °C, if extra annealing at 1200 °C was applied after every 100 h for the duration of 1 h, then the hardness indicator reduces from maximum 48 to below 24.\u3c/p\u3