Geometric constraint of mechanosensing by modification of hydrogel thickness prevents stiffness-induced differentiation in bone marrow stromal cells.

Extracellular matrix (ECM) stiffness is fundamental in cell division, movement and differentiation. The stiffness that cells sense is determined not only by the elastic modulus of the ECM material but also by ECM geometry and cell density. We hypothesized that these factors would influence cell traction-induced matrix deformations and cellular differentiation in bone marrow stromal cells (BMSCs).

Convergently evolved placental villi show multiscale structural adaptations to differential placental invasiveness.

Despite having a single evolutionary origin and conserved function, the mammalian placenta exhibits radical structural diversity. The evolutionary drivers and functional consequences of placental structural diversity are poorly understood. Humans and equids both display treelike placental villi, however these villi evolved independently and exhibit starkly different levels of invasiveness into maternal tissue (i.

Placental evolution from a three-dimensional and multiscale structural perspective.

The placenta mediates physiological exchange between the mother and the fetus. In placental mammals, all placentas are descended from a single common ancestor and functions are conserved across species; however, the placenta exhibits radical structural diversity. The selective pressures behind this structural diversity are poorly understood.

Depth profiling via nanoindentation for characterisation of the elastic modulus and hydraulic properties of thin hydrogel layers.

The accurate determination of the mechanical properties of hydrogels is of fundamental importance for a range of applications, including in assessing the effect of stiffness on cell behaviour. This is a particular issue when using thin hydrogel layers adherent to stiff substrate supports, as the apparent stiffness can be significantly influenced by the constraint of the underlying impermeable substrate, leading to inaccurate measurements of the elastic modulus and permeability of thin hydrogel layers. This study used depth profiling nanoindentation and a poroelastic model for spherical indentation to identify the elastic moduli and hydraulic conductivity of thin polyacrylamide (PAAm) hydrogel layers (∼27 μm-782 μm thick) on impermeable substrates.

Computational Modelling of Paracellular Diffusion and OCT3 Mediated Transport of Metformin in the Perfused Human Placenta.

Metformin is an antidiabetic drug, increasingly prescribed in pregnancy and has been shown to cross the human placenta. The mechanisms underlying placental metformin transfer remain unclear. This study investigated the roles of drug transporters and paracellular diffusion in the bidirectional transfer of metformin across the human placental syncytiotrophoblast using placental perfusion experiments and computational modelling.