Confinement induces internal flows in adherent cell aggregates.

During mesenchymal migration, F-actin protrusion at the leading edge and actomyosin contraction determine the retrograde flow of F-actin within the lamella. The coupling of this flow to integrin-based adhesions determines the force transmitted to the extracellular matrix and the net motion of the cell. In tissues, motion may also arise from convection, driven by gradients in tissue-scale surface tensions and pressures. However, how migration coordinates with convection to determine the net motion of cellular ensembles is unclear. To explore this, we study the spreading of cell aggregates on adhesive micropatterns on compliant substrates. During spreading, a cell monolayer expands from the aggregate towards the adhesive boundary. However, cells are unable to stabilize the protrusion beyond the adhesive boundary, resulting in retraction of the protrusion and detachment of cells from the matrix. Subsequently, the cells move upwards and rearwards, yielding a bulk convective flow towards the centre of the aggregate. The process is cyclic, yielding a steady-state balance between outward (protrusive) migration along the surface, and 'retrograde' (contractile) flows above the surface. Modelling the cell aggregates as confined active droplets, we demonstrate that the interplay between surface tension-driven flows within the aggregate, radially outward monolayer flow and conservation of mass leads to an internal circulation.

Active Regulation of Pressure and Volume Defines an Energetic Constraint on the Size of Cell Aggregates.

We explore the relationship between the nonequilibrium generation of myosin-induced active stress within the F-actin cytoskeleton and the pressure-volume relationship of cellular aggregates as models of simple tissues. We find that due to active stress, aggregate surface tension depends upon its size. As a result, both pressure and cell number density depend on size and violate equilibrium assumptions. However, the relationship between them resembles an equilibrium equation of state with an effective temperature. This suggests that bulk and surface properties of aggregates balance to yield a constant average work performed by each cell on their environment in regulating tissue size. These results describe basic physical principles that govern the size of cell aggregates.

Cell-Matrix Elastocapillary Interactions Drive Pressure-based Wetting of Cell Aggregates.

Cell-matrix interfacial energies and the energies of matrix deformations may be comparable on cellular length-scales, yet how capillary effects influence tis sue shape and motion are unknown. In this work, we induce wetting (spreading and migration) of cell aggregates, as models of active droplets onto adhesive substrates of varying elasticity and correlate the dynamics of wetting to the balance of interfacial tensions. Upon wetting rigid substrates, cell-substrate tension drives outward expansion of the monolayer. By contrast, upon wetting compliant substrates, cell substrate tension is attenuated and aggregate capillary forces contribute to internal pressures that drive expansion. Thus, we show by experiments, data-driven modeling and computational simulations that myosin-driven 'active elasto-capillary' effects enable adaptation of wetting mechanisms to substrate rigidity and introduce a novel, pressure-based mechanism for guiding collective cell motion.

Investigation into local cell mechanics by atomic force microscopy mapping and optical tweezer vertical indentation.

Investigating the mechanical properties of cells could reveal a potential source of label-free markers of cancer progression, based on measurable viscoelastic parameters. The Young's modulus has proved to be the most thoroughly studied so far, however, even for the same cell type, the elastic modulus reported in different studies spans a wide range of values, mainly due to the application of different experimental conditions. This complicates the reliable use of elasticity for the mechanical phenotyping of cells. Here we combine two complementary techniques, atomic force microscopy (AFM) and optical tweezer microscopy (OTM), providing a comprehensive mechanical comparison of three human breast cell lines: normal myoepithelial (HBL-100), luminal breast cancer (MCF-7) and basal breast cancer (MDA-MB-231) cells. The elastic modulus was measured locally by AFM and OTM on single cells, using similar indentation approaches but different measurement parameters. Peak force tapping AFM was employed at nanonewton forces and high loading rates to draw a viscoelastic map of each cell and the results indicated that the region on top of the nucleus provided the most meaningful results. OTM was employed at those locations at piconewton forces and low loading rates, to measure the elastic modulus in a real elastic regime and rule out the contribution of viscous forces typical of AFM. When measured by either AFM or OTM, the cell lines' elasticity trend was similar for the aggressive MDA-MB-231 cells, which were found to be significantly softer than the other two cell types in both measurements. However, when comparing HBL-100 and MCF-7 cells, we found significant differences only when using OTM.

The ethnic characteristics and prevalence of diabetes mellitus, hypertension and hyperlipidaemia in patients who underwent coronary artery bypass grafting in Hospital Universiti Kebangsaan Malaysia.

A retrospective study was done on 302 patients who had undergone coronary artery bypass grafting (CABG) in Hospital Universiti Kebangsaan Malaysia--46.0% were Chinese, 40.1% were Malays and 11.6% were Indians. Overall and irrespective of race and sex, the prevalence of diabetes mellitus, hypertension and hyperlipidaemia was 45.7%, 78.8% and 89.1% respectively indicating that hyperlipidaemia was the most prevalent risk factor amongst this cohort. The Indians had the highest prevalence of the three risk factors. The Chinese and the Malays most frequently presented with the combination of hypertension and hyperlipidaemia.