Collective Motion in Binary Cell Mixtures Formed by Cancer Trans-endothelial Migration

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蕭翌登(Yi-Teng Hsiao) 查詢紙本館藏

畢業系所

物理學系

論文名稱

(Collective Motion in Binary Cell Mixtures Formed by Cancer Trans-endothelial Migration)

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摘要(中)

細胞的集體運動可以在許多的生物過程中觀察到，如胚胎演化、傷口癒合、癌症轉移…等。在細胞層(上皮組織或內皮組織)裡，細胞的運動會透過主動的爬行(細胞骨架的聚合及解聚)、細胞與細胞間的交互作用(細胞連接)、及細胞與外在環境的交互作用(細胞粘著)表現一些合作運動。在這個的研究中，我們利用人類臍帶靜脈內皮細胞層模擬血管內皮，在加入不同特性的癌症細胞進行血管內皮穿透的過程(癌症轉移的過程之一)，藉此研究所形成之混合細胞層的動力學。原本的內皮細胞層就是一個強交互作用的多體系統，隨時間細胞密度增加會讓整體的運動漸漸變慢，內皮細胞的運動是微小的搖擺運動。加入不同特性的骨髓轉移鼻咽癌細胞(野生型:高流動性、突變型:高侵犯性)，癌細胞的入侵會破壞原本內皮細胞的細胞連接，但不同特性所帶來的影響不同。我們藉由縮時攝影和粒子影像測速分析法，可以探討形成過程、動力學變化、及內皮細胞的反應。我們可以觀察到動力學上的異質性。高流動性的野生型癌細胞讓內皮細胞的流動性增加，高侵犯性的突變型癌細胞藉由破壞細胞間的細胞連接，讓內皮細胞間的交互作用減少。

摘要(英)

Collective motion of cells is related to many biological processes, such as embryogenesis, tumorigenesis, wound healing, and cancer metastasis. Cells in the confluent cell layer exhibit cooperative motion through the interplay of active driving, adhesion, and mutual coupling. In this work, we use the human umbilical vein endothelial cells (ECs) monolayer as the base system. The binary cell mixture is formed by the trans-endothelial migration, which is one of the cancer metastasis processes. The ECs layer is a strongly coupled dense-packed many-body system. As increasing the cell density, the dynamics of the ECs can be slowed down. There are two types of the bone marrow metastasis nasopharyngeal carcinoma cell (BM1): the wild type (WT) with high motility and the mutant type (MT) with more invasive ability. Through the time-lapse observation and particle imaging velocimetry (PIV) analysis, the formation process, the dynamics, and the response of the ECs can be explored. It is found that the property of the cancer cell can affect the collective pattern and the formation process of the binary cell mixture. The dynamical heterogeneity can be observed. It can also induce the different response of the ECs. It is found that the rocking motion of the ECs layer are changed by high motility wild type (WT) BM1 cancer cell and more invasive mutant type (MT) BM1 cancer cell. WT induces the more persistent motion and MT reduces the couplings between cells through the cell-cell junction broken.

關鍵字(中)

★ 集體運動
★ 癌細胞

關鍵字(英)

★ Collective Motion
★ Cancer cell
★ Trans-endothelial Migration

論文目次

Abstract i
Acknowledgements iii
Content iv
List of Figures v
List of Tables x

Introduction 1
Background 7
2-1. Feature of many body systems 7
2-2. Cell structure 8
2-3. Cell movement 13
2-4. Collective motion of cells 15
2-5. Dynamical heterogeneity and structural rearrangement 18
Experiment and analysis 20
3-1. Cell Culture 21
3-2. Gelatin matrix assay 23
3-3. Binary cell mixture formation (trans-endothelial migration) 24
3-4. Observation system 27
3-5. Immunofluorescence staining 29
3-6. Data analysis 30
Result and discussion 36
4-1. Endothelial cells layer structure 36
4-2. Cancer cell type characteristic 38
4-3. Formation process of binary cell mixture 40
4-4. Cancer cell density effect 42
4-5. Collective behavior 44
4-6. Response of the endothelial cells 53
Conclusions and Future work 61

Bibliographies 65
Appendixes 68

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指導教授

溫偉源(Wei-Yen Woon)

審核日期

2017-1-3

推文