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 Dictyostellum 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM078586-08
Application #
8720784
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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) Emergent Collective Chemotaxis without Single-Cell Gradient Sensing. Phys Rev Lett 116:098101
Rappel, Wouter-Jan (2016) Cell-cell communication during collective migration. Proc Natl Acad Sci U S A 113:1471-3
Bhowmik, Arpan; Rappel, Wouter-Jan; Levine, Herbert (2016) Excitable waves and direction-sensing in Dictyostelium discoideum: steps towards a chemotaxis model. Phys Biol 13:016002
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
Kessler, David A; Levine, Herbert (2015) Scaling solution in the large population limit of the general asymmetric stochastic Luria-Delbrück evolution process. J Stat Phys 158:783-805
Loomis, William F (2015) Genetic control of morphogenesis in Dictyostelium. Dev Biol 402:146-61
Álvarez-González, Begoña; Meili, Ruedi; Bastounis, Effie et al. (2015) Three-dimensional balance of cortical tension and axial contractility enables fast amoeboid migration. Biophys J 108:821-32
Rosengarten, Rafael David; Santhanam, Balaji; Fuller, Danny et al. (2015) Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum. BMC Genomics 16:294

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