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:

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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University of California San Diego
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Levine, Herbert (2014) Learning physics of living systems from Dictyostelium. Phys Biol 11:053011
Loomis, William F (2014) Cell signaling during development of Dictyostelium. Dev Biol 391:1-16
Skoge, Monica; Yue, Haicen; Erickstad, Michael et al. (2014) Cellular memory in eukaryotic chemotaxis. Proc Natl Acad Sci U S A 111:14448-53
Knoch, Fabian; Tarantola, Marco; Bodenschatz, Eberhard et al. (2014) Modeling self-organized spatio-temporal patterns of PIP? and PTEN during spontaneous cell polarization. Phys Biol 11:046002
Camley, Brian A; Rappel, Wouter-Jan (2014) Velocity alignment leads to high persistence in confined cells. Phys Rev E Stat Nonlin Soft Matter Phys 89:062705
Tarantola, Marco; Bae, Albert; Fuller, Danny et al. (2014) Cell substratum adhesion during early development of Dictyostelium discoideum. PLoS One 9:e106574
Camley, Brian A; Zhang, Yunsong; Zhao, Yanxiang et al. (2014) Polarity mechanisms such as contact inhibition of locomotion regulate persistent rotational motion of mammalian cells on micropatterns. Proc Natl Acad Sci U S A 111:14770-5
Hu, Bo; Rappel, Wouter-Jan; Levine, Herbert (2014) How input noise limits biochemical sensing in ultrasensitive systems. Phys Rev E Stat Nonlin Soft Matter Phys 90:032702
Camley, Brian A; Zhao, Yanxiang; Li, Bo et al. (2013) Periodic migration in a physical model of cells on micropatterns. Phys Rev Lett 111:158102
Segota, Igor; Mong, Surin; Neidich, Eitan et al. (2013) High fidelity information processing in folic acid chemotaxis of Dictyostelium amoebae. J R Soc Interface 10:20130606

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