The final phase of the chemotactic process results in the actual movement of the cell. This movement involves a complex set of cellular processes and includes the generation of protrusive, retractive, and adhesive forces. The mechanisms underlying these forces are poorly understood, partially due to the lack of quantitative data. For example, it is unclear how Dlctyostellum cells adhere to the substrate, and how the substrate adhesiveness and rigidity affect cell motility. New experimental techniques, however, open up the possibility of examining the forces involved in cell migration and can provide quantitative data necessary for a deeper understanding of cell motility. Our goal in this project is two-fold: the first goal is to determine the forces at the substrate-cell interface and their role in cell motility using novel microfluidics techniques in combination with innovative substrates that allow for simultaneous fraction microscopy and Total Internal Reflection Fluorescence (TIRF) microscopy. The second goal is to use this experimental data to build a comprehensive computational model for cell motility that includes force generation, cell-substrate interactions, membrane properties and cell deformations. As in project 1 and 2, the experimental-computational interaction will be critical to achieving our goals. Specifically, we propose:

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM078586-07
Application #
8539014
Study Section
Special Emphasis Panel (ZRG1-CB-G)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
7
Fiscal Year
2013
Total Cost
$174,296
Indirect Cost
$61,847
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
Kulawiak, Dirk Alexander; Camley, Brian A; Rappel, Wouter-Jan (2016) Modeling Contact Inhibition of Locomotion of Colliding Cells Migrating on Micropatterned Substrates. PLoS Comput Biol 12:e1005239
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

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