Experiments using fluorescent reporters have shown that the spatial distribution of many signaling pathway components is altered following a change in the chemoattractant cAMP concentration. These changes occur during the first 0-10 sec after binding or unbinding of the ligand to the receptors. Within this time frame, the membrane closest to the cAMP source experiences an increase in certain signaling components while other components display an increased concentration at the membrane away from the source. Even though a large number of signaling components have been identified, the precise mechanisms of directional sensing remain unclear. To fully understand these mechanisms it is essential to obtain quantitative data using precisely controlled stimulations. To address these mechanisms, we propose to investigate the initial phase of the chemotaxis process using an approach in which the chemoattractant stimulus can be carefully controlled, both spatially and temporally. The results from these experiments will be integrated into models that, in turn, will guide the experiments. We believe that such interaction of modeling with experimentation is essential for making progress in understanding eukaryotic chemotaxis. Indeed, it is this interaction that has proven to be fruitful during the past 4 years.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
4P01GM078586-10
Application #
9134792
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
10
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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
Camley, Brian A; Zimmermann, Juliane; Levine, Herbert et al. (2016) Emergent Collective Chemotaxis without Single-Cell Gradient Sensing. Phys Rev Lett 116:098101
Zimmermann, Juliane; Camley, Brian A; Rappel, Wouter-Jan et al. (2016) Contact inhibition of locomotion determines cell-cell and cell-substrate forces in tissues. Proc Natl Acad Sci U S A 113:2660-5
Bastounis, Effie; Álvarez-González, Begoña; del Álamo, Juan C et al. (2016) Cooperative cell motility during tandem locomotion of amoeboid cells. Mol Biol Cell 27:1262-71

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