Following the gradient sensing phase, cells reorganize their internal components into a symmetry-broken configuration, resulting in an elongated cell with a clearly identifiable back, front, and side. This polarized state is coupled to motility through the formation of membrane extensions, pseudopodia, which occur mostly at the front of the cell. Using quantitative measurements on cells that are vertically restricted, we have determined that these pseudopodia are closely correlated with membrane areas (""""""""patches"""""""") of increased concentration of activated Ras, Ras-GTP. What remains unclear, however, is the role Ras-GTP plays in restricting the pseudopodia to the front of the cell. Furthermore, the mechanisms for the transient nature of the patches and pseudopodia are unclear. Finally, there is a vigorous and ongoing debate whether new pseudopodia split off existing ones via a specialized fip-splitting mechanism or whether new pseudopodia are created in a stochastic fashion, largely independent of the location of the existing pseudopod. The goal of this project will be to examine the mechanisms of cell polarity using microfluidics technology in combination with modeling efforts. The quantitative results from the experiments will be used to construct mathematical models. Conversely, through specific predictions, these models will guide the experiments. Again, we think that such two-way communication between experiments and modeling is essential in making progress in understanding the role of polarity in chemotaxis.

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Yue, Haicen; Camley, Brian A; Rappel, Wouter-Jan (2018) Minimal Network Topologies for Signal Processing during Collective Cell Chemotaxis. Biophys J 114:2986-2999
Camley, Brian A (2018) Collective gradient sensing and chemotaxis: modeling and recent developments. J Phys Condens Matter 30:223001
Tu, Yuhai; Rappel, Wouter-Jan (2018) Adaptation of Living Systems. Annu Rev Condens Matter Phys 9:183-205
Camley, Brian A; Rappel, Wouter-Jan (2017) Physical models of collective cell motility: from cell to tissue. J Phys D Appl Phys 50:
Camley, Brian A; Rappel, Wouter-Jan (2017) Cell-to-cell variation sets a tissue-rheology-dependent bound on collective gradient sensing. Proc Natl Acad Sci U S A 114:E10074-E10082
Rappel, Wouter-Jan; Edelstein-Keshet, Leah (2017) Mechanisms of Cell Polarization. Curr Opin Syst Biol 3:43-53
Camley, Brian A; Zhao, Yanxiang; Li, Bo et al. (2017) Crawling and turning in a minimal reaction-diffusion cell motility model: Coupling cell shape and biochemistry. Phys Rev E 95:012401
Loomis, William F (2016) A better way to discover gene function in the social amoeba Dictyostelium discoideum. Genome Res 26:1161-4
Camley, Brian A; Zimmermann, Juliane; Levine, Herbert et al. (2016) Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance. PLoS Comput Biol 12:e1005008
Rappel, Wouter-Jan (2016) Cell-cell communication during collective migration. Proc Natl Acad Sci U S A 113:1471-3

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