Dilatancy in slow granular flows

When walking on wet sand, each footstep leaves behind a temporarily dry impression. This counterintuitive observation is the most common illustration of the Reynolds principle of dilatancy: that is, a granular packing tends to expand as it is deformed, therefore increasing the amount of porous space. Although widely called upon in areas such as soil mechanics and geotechnics, a deeper understanding of this principle is constrained by the lack of analytical tools to study this behavior. Using x-ray radiography, we track a broad variety of granular flow profiles and quantify their intrinsic dilatancy behavior. These measurements frame Reynolds dilatancy as a kinematic process. Closer inspection demonstrates, however, the practical importance of flow induced compaction which competes with dilatancy, leading more complex flow properties than expected

Tumour heterogeneity promotes collective invasion and cancer metastatic dissemination.

Heterogeneity within tumour cell populations is commonly observed in most cancers. However, its impact on metastatic dissemination, one of the primary determinants of the disease prognosis, remains poorly understood. Working with a simplified numerical model of tumour spheroids, we investigated the impact of mechanical heterogeneity on the onset of tumour invasion into surrounding tissues. Our work establishes a positive link between tumour heterogeneity and metastatic dissemination, and recapitulates a number of invasion patterns identified in vivo, such as multicellular finger-like protrusions. Two complementary mechanisms are at play in heterogeneous tumours. A small proportion of stronger cells are able to initiate and lead the escape of cells, while collective effects in the bulk of the tumour provide the coordination required to sustain the invasive process through multicellular streaming. This suggests that the multicellular dynamics observed during metastasis is a generic feature of mechanically heterogeneous cell populations and might rely on a limited and generic set of attributes

Pressure sensing through Piezo channels controls whether cells migrate with blebs or pseudopods.

Blebs and pseudopods can both power cell migration, with blebs often favored in tissues, where cells encounter increased mechanical resistance. To investigate how migrating cells detect and respond to mechanical forces, we used a "cell squasher" to apply uniaxial pressure to Dictyostelium cells chemotaxing under soft agarose. As little as 100 Pa causes a rapid (<10 s), sustained shift to movement with blebs rather than pseudopods. Cells are flattened under load and lose volume; the actin cytoskeleton is reorganized, with myosin II recruited to the cortex, which may pressurize the cytoplasm for blebbing. The transition to bleb-driven motility requires extracellular calcium and is accompanied by increased cytosolic calcium. It is largely abrogated in cells lacking the Piezo stretch-operated channel; under load, these cells persist in using pseudopods and chemotax poorly. We propose that migrating cells sense pressure through Piezo, which mediates calcium influx, directing movement with blebs instead of pseudopods

A one-piece 3D printed flexure translation stage for open-source microscopy.

Open source hardware has the potential to revolutionise the way we build scientific instruments; with the advent of readily available 3D printers, mechanical designs can now be shared, improved, and replicated faster and more easily than ever before. However, printed parts are typically plastic and often perform poorly compared to traditionally machined mechanisms. We have overcome many of the limitations of 3D printed mechanisms by exploiting the compliance of the plastic to produce a monolithic 3D printed flexure translation stage, capable of sub-micron-scale motion over a range of 8 × 8 × 4 mm. This requires minimal post-print clean-up and can be automated with readily available stepper motors. The resulting plastic composite structure is very stiff and exhibits remarkably low drift, moving less than 20 μm over the course of a week, without temperature stabilisation. This enables us to construct a miniature microscope with excellent mechanical stability, perfect for time-lapse measurements in situ in an incubator or fume hood. The ease of manufacture lends itself to use in containment facilities where disposability is advantageous and to experiments requiring many microscopes in parallel. High performance mechanisms based on printed flexures need not be limited to microscopy, and we anticipate their use in other devices both within the laboratory and beyond.We would like to thank Paula Rudall (Jodrell Laboratory, Royal Botanic Gardens, Kew, UK) for preparing the Pollia condensata samples. RWB was supported by Research Fellowships from Queens’ College, Cambridge and the Royal Commission for the Exhibition of 1851, and partial support was provided by EPSRC EP/L027151/1, the University Teaching and Learning Innovation Fund and the SynBioFund initiative.This is the final version of the article. It first appeared from AIP Publishing via http://dx.doi.org/10.1063/1.4941068 Data supporting this publication is available at http://www.repository.cam.ac.uk/handle/1810/253294. Design files and assembly instructions are available at http://docubricks.com/projects/ openflexure-microscope

Contact dynamics in a gently vibrated granular pile

We use multi-speckle diffusive wave spectroscopy (MSDWS) to probe the micron-scale dynamics of a granular pile submitted to discrete gentle taps. The typical time-scale between plastic events is found to increase dramatically with the number of applied taps. Furthermore, this microscopic dynamics weakly depends on the solid fraction of the sample. This process is strongly analogous to the aging phenomenon observed in thermal glassy systems. We propose a heuristic model where this slowing down mechanism is associated with a slow evolution of the distribution of the contact forces between particles. This model accounts for the main features of the observed dynamics.Comment: 4 pages, 4 figure

Spatial heterogeneity of cell-matrix adhesive forces predicts human glioblastoma migration.

BACKGROUND: Glioblastoma (GBM) is a highly aggressive incurable brain tumor. The main cause of mortality in GBM patients is the invasive rim of cells migrating away from the main tumor mass and invading healthy parts of the brain. Although the motion is driven by forces, our current understanding of the physical factors involved in glioma infiltration remains limited. This study aims to investigate the adhesion properties within and between patients' tumors on a cellular level and test whether these properties correlate with cell migration. METHODS: Six tissue samples were taken from spatially separated sections during 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery. Navigated biopsy samples were collected from strongly fluorescent tumor cores, a weak fluorescent tumor rim, and nonfluorescent tumor margins. A microfluidics device was built to induce controlled shear forces to detach cells from monolayer cultures. Cells were cultured on low modulus polydimethylsiloxane representative of the stiffness of brain tissue. Cell migration and morphology were then obtained using time-lapse microscopy. RESULTS: GBM cell populations from different tumor fractions of the same patient exhibited different migratory and adhesive behaviors. These differences were associated with sampling location and amount of 5-ALA fluorescence. Cells derived from weak- and nonfluorescent tumor tissue were smaller, adhered less well, and migrated quicker than cells derived from strongly fluorescent tumor mass. CONCLUSIONS: GBM tumors are biomechanically heterogeneous. Selecting multiple populations and broad location sampling are therefore important to consider for drug testing

Islands of conformational stability for Filopodia

Filopodia are long, thin protrusions formed when bundles of fibers grow outwardly from a cell surface while remaining closed in a membrane tube. We study the subtle issue of the mechanical stability of such filopodia and how this depends on the deformation of the membrane that arises when the fiber bundle adopts a helical configuration. We calculate the ground state conformation of such filopodia, taking into account the steric interaction between the membrane and the enclosed semiflexible fiber bundle. For typical filopodia we find that a minimum number of fibers is required for filopodium stability. Our calculation elucidates how experimentally observed filopodia can obviate the classical Euler buckling condition and remain stable up to several tens of . We briefly discuss how experimental observation of the results obtained in this work for the helical-like deformations of enclosing membrane tubes in filopodia could possibly be observed in the acrosomal reactions of the sea cucumber Thyone, and the horseshoe crab Limulus. Any realistic future theories for filopodium stability are likely to rely on an accurate treatment of such steric effects, as analysed in this work