1. Collective behaviors in living cell populations

One example of such new physics may lie in the emergence of collective behaviors in early developing cell populations and cell tissues. Cells are at the same time an ‚??active living agent‚?? while they are exposed to external chemical signaling and mechanical force fields. Combining these two properties, individuality and field dependence, is a fundamental issue across all the physical sciences that has not been resolved, neither theoretically nor experimentally. My laboratory approaches this question two fold: we study the emergence of multicellularity in starved cell populations of the social amoeba Dictyostelium, and we try to extract the mechanical tissue properties during the earliest stages of developing fly embryos.

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For the amoebae project, we have developed a novel optical sensor (based on Foerster-Resonance-Energy- Transfer technology), which allows for direct fluorescence measurements of intra-cellular signaling in develop- ing cell populations. We are currently designing cellular environments based on microfluidic technology to obtain a greater handle on the extracellular space (i.e. extracellular signaling molecule concentration measurements, generation of temporal and spatial concentration waves), allowing us to probe living cells at the single- and multi-cellular levels with great control. Further we are developing a phenomenological theoretical model in collaboration with Pankaj Mehta (Boston University/Physics) to bridge the gap between single cell properties and collective multicellular phenomena. In order to connect this top-down approach back to molecular detail of the cellular signaling cascade, we are measuring the single-cell signaling properties of various signaling mutants that display phenotypes at the macroscopic level. To this end, we are collaborating with Ted Cox in the Molecular Biology department in order to take advantage of his large mutagenesis database, which we combine with our optical sensors.

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The tissue mechanics project necessitates highly spatially and temporally resolved dynamic data of de- veloping fly embryos. My laboratory has set up microscopy to capture movies of living tissue in which individual nuclei are labeled optically. In collaboration with Andrea Liu (UPenn/Physics) and Lisa Manning (Syracuse/Physics) we are developing analysis tools to extract mechanical tissue properties from these movies. Preliminary re- sults generated by a novel cell tracking software suggest that mitotic divisions in Drosophila occur in a series of waves initiated in an excitable medium, i.e. one where waves are actively regenerated in the material. Our Dictyostelium work has also suggested that multicellular signaling proceeds by excitable, self-generated waves. The plan is to model both the mechanical and biochemical cell-cell (or nuclei-nuclei) interactions in these systems, to understand the mechanisms for wave propagation and tease apart the role of these excitable waves in multicellular organization.


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