2018 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 | fast-crawling cells / mechanosensitivity |
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| Outline of Annual Research Achievements |
We have concluded our initial study on the mechanosensitivity of crawling cells over cyclically stretched substrates and succeeded in publishing our results in Soft Matter. At the moment, there is a debate over whether the reorientation observed experimentally is due to the passively stored elastic energy of the cell, or the forces on the focal adhesion sites. Models based on either of these assumptions provide the same level of agreement with experiments, making it difficult to distinguish which effect is more important. For this initial study, we focused on the role played by the focal adhesions and investigated how they could account for the experimental observations.
We focused on fast-crawling cells, for which the coupling between shape/motility cannot be ignored and which are difficult to describe using standard models. We showed how an asymmetry in the adhesion dynamics (particularly in the detachment rate) during loading/unloading can be used to selectively reorient the cells. The origin of the reorientation was found to be the induced non-symmetric stability/instability of the actin polymerization. We realized that the asymmetry required to drive this reorientation could be caused either by the inherent properties of the cell or by the stretching protocol. To test these hypotheses and help us to understand the internal dynamics of the cell, we have proposed additional experiments.
We have also studied the dynamics over patterned substrates and discovered that the topology can be used to control the dynamics of the cells (i.e, ballistic versus diffusive-type motion).
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
We are currently improving our model to be able to provide more quantitative comparisons with experiments. In particular, and in response to objections raised during the review process of our paper, we are including the elastic response of the cell (in particular, the membrane tension feedback into the actin polymerization rate and the bending rigidity). In parallel, we are also investigating the use of a discrete and stochastic adhesion model. Unfortunately, this has taken more time than initially planned.
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| Strategy for Future Research Activity |
We will finish the implementation of the improved model and reconsider the dynamics of cells on cyclically stretched and patterned substrates. This will allow us to distinguish between the roles of adhesion and elasticity, over which there is an ongoing debate. In addition, this will also allow us to investigate how the dynamics of different cell types can be controlled.
If possible, we will implement the cell-division into our model and study the proliferation of cell colonies. As a counter-measure, if we are unable to accomplish this task in the required time, we have started collaborating with colleagues to study systems of proliferating cells using a simpler particle-based model (as opposed to our detailed phase-field description).
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| Causes of Carryover |
After a detailed cost/performance analysis, I have purchased a workstation that was less expensive than the one I had initially considered. This has allowed me to save money that I can more efficiently use during the next fiscal year for the necessary materials, equipment, and computational resources.
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