2020 Fiscal Year Research-status Report
A mechanical study of lumen formation through membrane bleb regulation under hemodynamic influence
| Project/Area Number |
20K20190
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
MaungYe SweSoe 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (60866408)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Microhemodynamics / Hematocrit asymmetry / Wall shear stress / Vascular morphogenesis / Membrane blebbing / RBC mechanics / Endothelial mechanics / Vascular mechanics |
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| Outline of Annual Research Achievements |
To investigate the link between flow forces and apical membrane blebbing in a developing lumen, I have developed a computational fluid dynamics (CFD) model of blood flow in the zebrafish embryo. Variation in wall shear stress and luminal pressure can be discussed in relation to vascular network connectivity, vessel morphology, network partitioning asymmetries of red blood cell (RBC) perfusion and flow pulsation. Using this CFD model, I vary the morphology of the vascular network to represent flow in mutant phenotype Marcksl1 overexpression (OE) where extensive apical blebbing occurs versus Marcksl1 depletion (DE) phenotype where vessel diameters are reduced in concomitance with the bleb inhibition. The results and discussion are being prepared for submission to PLOS Computational Biology.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
Construction of the RBC flow model in the CFD technique had some unforeseen challenges with the RBC to luminal wall contact and collision physics. This methodology challenge has since been overcome.
Additionally, the covid19 situation in 2020 delayed the conduct of planned experiments for measurement of apical membrane tension and actomyosin dynamics during lumen formation via lumen expansion. This activity has been postponed to be conducted in the late half of 2021.
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| Strategy for Future Research Activity |
1) Submit paper on CFD analysis of network hemodynamics in wildtype, Marcksl1 OE and Marcksl1 DE mutant zebrafish.
2) Perform experiments of apical membrane tension measurement and actomyosin dynamics quantification.
3) Construct 2-layer membrane computational model of endothelial cell undergoing apical membrane blebbing in the vascular environment
4) Construct the computational models of actomyosin transport and membrane bleb regulation
5) Combine models to demonstrate lumen expansion under the multiple factors of actomyosin assembly and hemodynamic force variation due to network flow effects
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| Causes of Carryover |
The majority of the planned budget was consumables for planned experiments. The consumables budget was unused since experiments were postponed to the next fiscal year due to covid19 disruptions to physical working conditions within the lab.
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