Rupture strength of living cell monolayers.

To fulfil their function, epithelial tissues need to sustain mechanical stresses and avoid rupture. Although rupture is usually undesired, it is central to some developmental processes, for example, blastocoel formation. Nonetheless, little is known about tissue rupture because it is a multiscale phenomenon that necessitates comprehension of the interplay between mechanical forces and biological processes at the molecular and cellular scales.

Fracture in living tissues.

During development and in adult physiology, living tissues are continuously subjected to mechanical stresses originating either from cellular processes intrinsic to the tissue or from external forces. As a consequence, rupture is a constant risk and can arise as a result of excessive stresses or because of tissue weakening through genetic abnormalities or pathologies. Tissue fracture is a multiscale process involving the unzipping of intercellular adhesions at the molecular scale in response to stresses arising at the tissue or cellular scale that are transmitted to adhesion complexes via the cytoskeleton.

Theoretical analysis of inducer and operator binding for cyclic-AMP receptor protein mutants.

Allosteric transcription factors undergo binding events at inducer binding sites as well as at distinct DNA binding domains, and it is difficult to disentangle the structural and functional consequences of these two classes of interactions. We compare the ability of two statistical mechanical models-the Monod-Wyman-Changeux (MWC) and the Koshland-Némethy-Filmer (KNF) models of protein conformational change-to characterize the multi-step activation mechanism of the broadly acting cyclic-AMP receptor protein (CRP). We first consider the allosteric transition resulting from cyclic-AMP binding to CRP, then analyze how CRP binds to its operator, and finally investigate the ability of CRP to activate gene expression.

Integration of actomyosin contractility with cell-cell adhesion during dorsal closure.

In this work, we combine genetic perturbation, time-lapse imaging and quantitative image analysis to investigate how pulsatile actomyosin contractility drives cell oscillations, apical cell contraction and tissue closure during morphogenesis of the amnioserosa, the main force-generating tissue during the dorsal closure in Drosophila We show that Myosin activity determines the oscillatory and contractile behaviour of amnioserosa cells. Reducing Myosin activity prevents cell shape oscillations and reduces cell contractility. By contrast, increasing Myosin activity increases the amplitude of cell shape oscillations and the time cells spend in the contracted phase relative to the expanded phase during an oscillatory cycle, promoting cell contractility and tissue closure.

Emergent material properties of developing epithelial tissues.

Background: Force generation and the material properties of cells and tissues are central to morphogenesis but remain difficult to measure in vivo. Insight is often limited to the ratios of mechanical properties obtained through disruptive manipulation, and the appropriate models relating stress and strain are unknown. The Drosophila amnioserosa epithelium progressively contracts over 3 hours of dorsal closure, during which cell apices exhibit area fluctuations driven by medial myosin pulses with periods of 1.

Contractile and mechanical properties of epithelia with perturbed actomyosin dynamics.

Mechanics has an important role during morphogenesis, both in the generation of forces driving cell shape changes and in determining the effective material properties of cells and tissues. Drosophila dorsal closure has emerged as a reference model system for investigating the interplay between tissue mechanics and cellular activity. During dorsal closure, the amnioserosa generates one of the major forces that drive closure through the apical contraction of its constituent cells.