Morphogenesis, which is the process by which multi-cellular organisms acquire their "shape", is the ultimate challenge in the study of pattern formation. Morphogenesis executes a genetically encoded developmental program, and much of the prior work has been focused on the pattern of gene expression and the molecular signals that control it. Yet because morphogenesis involves spatial rearrangement and flow of cells, physical interaction of cells within tissue plays an important role. This project will address the role of mechanical stress in coordinating cellular and sub-cellular processes with the global organization and dynamics of tissues. The proposed work will involve intra- and extramural collaborations with experimental labs, funded by other sources. As a member of the Physics Department, the PI works with physics students encouraging and guiding their research on biology problems. As a member of the Kavli Institute for Theoretical Physics (KITP), the PI coordinates the Interdisciplinary Biology Initiative that runs programs designed to break barriers between disciplines. The PI also co-directs the Santa Barbara Advanced School of Quantitative Biology (SBASQB), which holds an annual advanced Summer Research Lab course on the UCSB campus and attracts young scientists with Physics and/or Biology backgrounds from the US and around the world.
The PI will formulate and study a model of epithelial tissue mechanics in conjunction with quantitative analysis of experimental data for several prototypical steps of embryonic and larval development of a fruit fly. In contrast to the familiar viscoelasticity of passive materials, which are elastic at short times but flow relaxing the stress at long times, epithelial tissues can flow while remodeling at short times, yet at long times behave as a solid - an "Active Solid" supporting static external stress. This can be understood by invoking the activity of myosin motors and their ability to redistribute in a tension-dependent manner, which results in interesting and unusual response properties of this Active Solid state of living matter. The proposed work will apply these ideas to morphogenetic processes on large and small scales. On the large scale, the proposed work will develop a description of the global "Morphogenetic Flow" that rearranges tissues during gastrulation of Drosophila embryo, and aim to uncover the mechanism controlling the spatiotemporal pattern of myosin activation that defines the flow. On the smaller scale, it will model the mechanism of cell rearrangement during the larval stage of Drosophila eye development that leads to the formation of an ordered "ommatidial crystal" making up the fly's compound eye. The project will: 1) Develop the Active Solid Model (ASM) of epithelial tissue mechanics describing its fluid-like ability to rearrange that coexists with the ability to support steady external stress. Specifically: i) formulate a model of mechanical feedback on myosin recruitment, coupling myosin dynamics to the cytoskeletal stress and rate of strain; ii) derive a consistent continuum theory; iii) define quantitative predictions for the dynamic response to mechanical perturbations; iv) test and refine the model by comparing the predicted response with experimental data for Drosophila tissues. 2) Develop a quantitative description of global morphogenetic flow in Drosophila embryo in terms of myosin controlled continuous transformation of mechanical equilibria. The project will use the ASM framework to disentangle genetically controlled patterning of myosin activity from the effects of passive transport and mechanical feedback. Emerging hypotheses regarding relevant gene expression patterns will be tested by suitably designed experiments. 3) Develop a mechanical model to describe the observed rearrangement of cells leading to the ordered array of receptor-cells during Drosophila eye development. This project will build on the quantitative analysis of the new time-lapse imaging data, which documents the dynamics of "ommatidial crystal" formation with sub-cellular resolution.
