Biomechanics of Morphogenesis

Project Summary: Physical mechanical processes are central to the morphogenesis of embryos and their organs. The goal of this proposal is to apply a multi-scale analysis of the mechanics of convergent extension, identifying biomechanical mechanisms that establish passive tissue properties such as stiffness as well as active processes that generate forces of extension, regulate cell behaviors and tissue deformation, and how passive mechanics and active force generating processes are coordinated within the frog embryo. Studies outlined in this proposal will answer: (1) What are the molecular regulators of cell cortex mechanics and cell shape change during dorsal axis elongation? We previously identified a form of "mechanical maturation" as cells transition from undifferentiated progenitor to early ectodermal, mesodermal, or endodermal cell. To answer this question we will identify regulators and test their role in cell cortex density and cell shape to elasticity and force production. (2) How is force production coordinated from early to late elongation? Simulations and live-imaging suggest cooperativity between anisotropic tissue tension and polarization of the cytoskeleton, "cytoskeletal focusing". To answer this question we will quantify emergent focusing of actomyosin dynamics and test roles for actin polymerization and myosin transport in elongation. (3) What is the role of mechanical strain energy in sustaining convergent extension? Preliminary data reveals the existence of "mechanical memory" in dorsal tissues to store and use mechanical strain energy during convergent extension. This aim will quantify mechanical memory and the role of strain energy loss, e.g. strain energy dissipation in axis elongation. Results from this project will complement ongoing efforts to identify the molecular regulators of morphogenesis by providing a conceptual framework developing new hypotheses of morphogenesis and bioengineering tools to test them. The significance of our work provides researchers a more complete understanding of the contribution of cell- and tissue-mechanics to development, to understand the role of tissue mechanics in oncogenesis, and to provide fundamental physical principles for future functional tissue engineers.