2019 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 – 2021-03-31
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| Keywords | cell migration / cell proliferation / crawling cells / mechanosensitivity |
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| Outline of Annual Research Achievements |
As part of an ongoing collaboration, we have published two papers that used a particle-based model to study (1) the collective migration and (2) the proliferation of cell colonies. In the first paper, we showed how deformable cells could use shape-oscillations to perform local rearrangements that lead to synchronized collective motion, even in the absence of direct cell-cell signaling. In the second paper, we investigated the role of contact-inhibition on the proliferation of cells. In particular, we found two distinct regimes: at short times, the dynamics of the colony is governed by the proliferation rate, whereas at long times it is governed by the migration speed of the cells. Our results are in good qualitative agreement with experimental findings.
The above mentioned studies on the collective dynamics have been performed using a 'simple' particle-based model (as opposed to our preferred phase-field model) because of computational simplicity, particularly when considering proliferating cells. However, we have continued the development of our detailed phase-field model. We have finished implementing the membrane tension feedback and bending rigidity into the model, and will explore how they affect the mechanosensitive response of the cells.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
We finished implementing the membrane tension feedback and bending rigidity into our phase-field model, but because of the computational complexity involved, this took a much longer time then we anticipated. In particular, computing the higher-order terms associated with the curvature and tension required us to use different numerical techniques. However, we were finally able to reproduce previous results (Physica D. 318-319, 26-33, 2016), thus validating our implementation. This has allowed us to start simulating the dynamics of cells through complex heterogeneous environments, such as arrays of pillars, in order to investigate their use as cell sorting assays. Preliminary findings show that the geometry of the patterns can be used to control the cells, depending, for example, on the polymerization strength or the rigidity of the membrane.
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| Strategy for Future Research Activity |
We will use our updated phase-field model to study the role of the membrane elasticity on the mechanosensitivity of crawling cells. This will allow us to provide a more realistic description of crawling cells. In particular, we are interested in investigating how to control the dynamics of different types of cells (e.g., through stretching or patterning of the substrate, or through the arrangement of micro-pillars). The work required for this can be performed using the equipment and tools that we have already developed or purchased. We will also continue our collaboration to study the collective dynamics of proliferating cells using the simpler particle-based model.
We have requested an extension of the project due to difficulties caused by the COVID-19 outbreak. We will use the remaining budget to attend an international conference in order to present our research to the general physics community (APS March Meeting 2021).
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| Causes of Carryover |
Due to the COVID-19 outbreak, we were not able to carry out our planned activities. In particular, we were due to participate in two conferences, one national (Physical Society of Japan March Meeting) and one international (American Physical Society March Meeting), that were cancelled at the last minute. Due to this unforeseen event, we requested an extension into the next Fiscal year (2020). We will use the remaining funds to attend the next iteration of the APS March meeting and advertise our research achievements to the international physics community.
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