捲曲細胞中細胞核拉伸應變之衰減

Nuclear Strain Attenuation in Wavy Cells

胡安妮(ON-NEI WU)

指導教授 ： 趙本秀

國立臺灣大學/工學院/醫學工程學研究所/碩士(2018年)

https://doi.org/10.6342/NTU201804223

摘要

人體中許多組織如韌帶、血管等，都含有豐富的膠原蛋白纖維，這些捲曲的纖維組織其中之細胞也呈現扁平而彎曲的型態。近年細胞核的研究文獻指出細胞核的型態改變對後續基因的表現、轉譯有莫大的影響，本研究主要探討細胞型態對核應變的影響。當細胞培養在捲曲纖維上作拉伸時會隨著纖維被拉扯，變成直線。我們進一步利用微印壓技術做出直線和曲線的纖連蛋白基質控制細胞生長型態；並發展出可供顯微即時觀察的拉伸反應器，對細胞做單軸向拉抻。結果發現在捲曲細胞中細胞核相較直線細胞所受之應力明顯衰減，但在抑制肌凝蛋白後此應力卻會增加。並由免疫染色發現細胞型態會影響zyxin，靜態拉伸會促使捲曲細胞中的zyxin從核輸出，而直線細胞則反之，可見細胞型態會控制細胞對外力刺激的感受。

關鍵字

細胞核 ； 肌動蛋白 ； 活細胞影像 ； 力生物學 ； 細胞型態

並列摘要

In many collagen-rich tissues, such as vascular wall, ligament, and tendons, the fibrillary extracellular matrix is organized in a wavy structure, known as crimp. The embedded cells and their nuclei follow this structure and have a wavy morphology. Studies have shown that chromatin organization and some gene expression might be regulated by nuclear morphology. We are interested in how cell geometry regulate nuclear response upon stretch. When mesenchymal stem cells (MSCs) were stretched on wavy electrospun fibers, we observed that the cell was straightened rather than elongated. In order to have better control of cell morphology, MSCs were seeded on PDMS membranes microcontact-printed with fibronectin lines and examined real-time on a stretching bioreactor. Intranuclear Lagrangian strain field revealed that wavy cell geometry caused significant nuclear strain attenuation and this phenomenon is regulated by myosin. In addition, zyxin was exported form nuclei in wavy cells whereas the opposite trend was observed in straight cells. Our results indicated that cell morphology regulate stretch-induced nuclear mechanotransduction.

並列關鍵字

Nuclear mechanics ； actin ； live cell imaging ； zyxin ； mechanotransduction ； cell shape

參考文獻

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