2017 Fiscal Year Research-status Report
Minimal Physical Model of Crawling and Dividing Cells
| Project/Area Number |
17K17825
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| Research Institution | Kyoto University |
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Principal Investigator |
MOLINA JOHN 京都大学, 工学研究科, 助教 (20727581)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | crawling cells / substrate crawling / mechanosensitivity / phase field modeling |
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| Outline of Annual Research Achievements |
In light of recent experimental works, which have shown the cell-specific response of cells crawling on periodically stretching substrates, we decided to modify the research plan and have focused FY29 on studying this mechanosensitivity. Originally, such a study was planned for FY30.
We have reformulated the mathematical model of Ziebert et al. to describe the motion of cells crawling on periodically stretched substrates. We have successfully implemented this model and obtained promising results. We have shown that by tuning the coupling between the adhesion dynamics and the deformation of the substrate, the cells can be made to align either parallel/perpendicular to the direction of stretching. In particular, we have considered cells that "resist" being stretched or compressed too rapidly, in order to model the different mechanical properties of the actin-networks inside cells (e.g., the presence or absence of stress fibers). In this way, we have observed a rich phase diagram for the cell dynamics, as a function of cell type and the frequency and amplitude of the stretching. This will help us to explain the experimentally observed behavior, where different types of cells can show different alignment, depending on how strong and how fast the substrate is being deformed.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
We have successfully implemented the model and performed simulations of a cell crawling on a periodically stretched substrate. We have extensively explored the parameter space for the cell and substrate dynamics and obtained many promising results. Unfortunately, explaining these results has proven to be more difficult and has slightly delayed our progress. We are now focused on using a simplified theoretical description that will give us a predictive insight into how the cell-substrate coupling can explain the preferential orientation (parallel or perpendicular) observed in our simulations as well as in experiments. We believe that such a theoretical explanation is crucial to increase the impact factor of our work.
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| Strategy for Future Research Activity |
First, in the short term, we will conclude our work on mechanosensitivity by finding a theoretical explanation for the preferential alignment of the cells. This study on the cell-specific dynamics was originally planned for FY30, but has mostly been performed in FY29. The original plan for FY29 was to implement cell division using a hybrid continuum-particle description. However, before cell-division, we have realized that two aspects should be considered in order to provide a more realistic description of crawling cells: 1) the discrete nature of the adhesion sites and 2) the stochastic nature of the cell dynamics. We will focus on this in the medium term (FY30), and in the long term (FY31) we will return to incorporate cell division and study many-cell systems as originally intended.
In parallel, there are many promising phenomena and applications that can be considered with our model. Two examples which we are starting to consider are (1) the dynamics of cells on patterned substrates and (2) they dynamics of cells on curved substrates. We will now try to develop collaborations with experimental groups performing these types of experiments.
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| Causes of Carryover |
During the first year I focused on implementing and testing my simulation code, for this, I could use the available computational facilities in my lab. For this reason, I delayed purchasing a workstation or buying time on the university supercomputer, as initially planned. These two items accounted for most of my budget for FY29, but will instead be purchased during FY30.
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