Active wetting of epithelial tissues

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between 2D epithelial monolayers and 3D spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting --- a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression

Cortical cell stiffness is independent of substrate mechanics

Cortical stiffness is an important cellular property that changes during migration, adhesion and growth. Previous atomic force microscopy (AFM) indentation measurements of cells cultured on deformable substrates have suggested that cells adapt their stiffness to that of their surroundings. Here we show that the force applied by AFM to a cell results in a significant deformation of the underlying substrate if this substrate is softer than the cell. This ‘soft substrate effect’ leads to an underestimation of a cell’s elastic modulus when analysing data using a standard Hertz model, as confirmed by finite element modelling and AFM measurements of calibrated polyacrylamide beads, microglial cells and fibroblasts. To account for this substrate deformation, we developed a ‘composite cell–substrate model’. Correcting for the substrate indentation revealed that cortical cell stiffness is largely independent of substrate mechanics, which has major implications for our interpretation of many physiological and pathological processes

The influence of preload and heart rate on Doppler echocardiographic indexes of left ventricular performance: comparison with invasive indexes in an experimental preparation.

We evaluated the ability of Doppler echocardiography to assess left ventricular performance in six open-chest dogs studied under various conditions. Intravenous infusions of nitroglycerin were used to vary preload, atrial pacing was used to control heart rate, and changes in inotropic state were induced by two different doses of dobutamine (5 and 10 micrograms/kg/min iv) and by administration of propranolol (1 mg/kg iv). Left ventricular anterior wall myocardial segment length was used as an index of preload. Maximum aortic blood flow, peak acceleration of aortic blood flow, and dP/dt were measured with an electromagnetic flow probe around the ascending aorta and a high-fidelity pressure transducer in the left ventricle. A continuous-wave Doppler transducer applied to the aortic arch was used to measure peak aortic blood velocity, mean acceleration, time to peak velocity, and the systolic velocity integral. The differences between mean values obtained under different inotropic conditions were significant at the p less than .01 level for peak velocity and at the p less than .05 level for mean acceleration. Within a given animal, Doppler measurements of peak velocity correlated very closely with maximum aortic flow (r = .96), maximum acceleration of aortic flow (r = .95), and with maximum dP/dt (r = .92). Mean acceleration measured by Doppler echocardiography also correlated very closely with conventional indexes, but was subject to greater interobserver variability. Doppler measurements of time to peak and the systolic velocity integral correlated less well with conventional hemodynamic indexes.(ABSTRACT TRUNCATED AT 250 WORDS)</jats:p