- 學位論文
細胞週期進程M期收縮環的模擬及其在細胞集體遷移中的應用
Simulation of Contraction Ring in M Phase of Cell Cycle Progression and Application to Collective Cell Migration
摘要
人工角膜可用於填補角膜捐贈的短缺，然而聚合物製成之人工角膜仍有排斥疑慮。今藉由組織工程以自體細胞培養之可避免此問題，然而人工培養細胞仍存在不確定性。為了解決此問題，先前藉由改良Odde學者之細胞遷移理論模型，加入Keren學者的膜力理論，建構出新的細胞遷移模型，已分析多個細胞之間力學的交互作用。然先前細胞遷移模型僅模擬固定數目的多顆細胞，探討其遷移及排列情形；未考慮細胞培養時的細胞週期進行成長、分裂等行為。為使模型更加完善，本研究在原模型裡增加細胞週期控制系統，做為控制細胞行為的依據。並依據現有研究理論，我們加入成長、分裂、感測周遭空間大小等功能，以建立更完整的細胞遷移模型。模擬結果顯示：分裂之新細胞對其他細胞遷移時的平衡位置有影響，我們藉由參考布朗運動的分析方法，驗證新增功能之細胞遷移模型表現出足夠的隨機性，並干擾既有細胞的運動。本研究的模擬部分，我們參考細胞分裂數值模擬流程(Seunggyu Lee)，藉由投影法(Projection method, Chorin)和沉浸邊界法，再以數值方法計算細胞分裂時收縮環的收縮情形，並嘗試以不同網格排列方式進行運算。受限於MATLAB的記憶體極限，本研究的模擬的結果仍符合實驗觀測。研究貢獻在於將先前之細胞遷移模型，從力學分析提升至能進行細胞分裂的培養模擬，並加入之細胞週期的時間控制機制作為往後新增細胞行為之框架。我們更進一步進行細胞分裂數值模擬探討與其相關計算細節之探索。
並列摘要
Artificial cornea is potentially satisfied shortages of corneal donation, but artificial cornea made by polymer still has disadvantage. Nowadays, tissue engineering helps avoid this problem by culturing autologous cells, but uncertainties on culturing, especial artificial cornea, are concerned. In order to solve this problem, our cell migration model has been constructed from Odde’s cell migration model and from Keren’s membrane force theory to analyze the mechanical interaction between multiple cells. However, our previous cell migration model only simulated a fixed number of cells and analyzed their migration and arrangement, and it didn’t consider growth and cytokinesis in the cell cycle during culturing. To complete this model, we added a timer to the original model as a basis for controlling cell itself behavior. Accordingly to other researches, we developed functions such as growth, cytokinesis, and sensing the size of the surrounding space to complete cell migration performance. The simulation results showed that the new cells divided have an effect on the balance position among others. From the Brownian motion viewpoint, the sufficient randomness after adding new cell and interference with the movement of existing cells were capable and satisfied in our migration model. For details of the simulation, applying the cytokinesis numerical simulation process (Seunggyu Lee) and using the projection method (Chorin) and the immersed boundary method, we calculated the contraction of the contractile ring during cytokinesis with various meshes in simulation. Under the limitation of memory of the software MATLAB, the simulation results were in line with experimental observations. The contribution of our study is to upgrade the previous cell migration model from mechanical analysis to simulation of artificial cell culture. Thus the added cell cycle control system can be used as a framework for new cell behaviors in the future. We also further explored the numerical simulation of cytokinesis and its related computational details.