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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 趙本秀 | zh_TW |
| dc.contributor.advisor | Pen-Hsiu Grace Chao | en |
| dc.contributor.author | 温新民 | zh_TW |
| dc.contributor.author | Shin-MIn Wen | en |
| dc.date.accessioned | 2026-08-11T16:20:06Z | - |
| dc.date.available | 2026-08-12 | - |
| dc.date.copyright | 2026-08-11 | - |
| dc.date.issued | 2026 | - |
| dc.date.submitted | 2026-07-31 00:00:00 | - |
| dc.identifier.citation | [1] S.M. Wen, W.C. Wen, P.G. Chao, Zyxin and actin structure confer anisotropic YAP mechanotransduction, Acta Biomater 152 (2022) 313-320.
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Beckerle, Mechanical stress triggers nuclear remodeling and the formation of transmembrane actin nuclear lines with associated nuclear pore complexes, Mol Biol Cell 31(16) (2020) 1774-1787 | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/103388 | - |
| dc.description.abstract | 人體中的細胞會因為組織結構與功能需求而持續受到具有非等向的變形，例如肌腱細胞和肌肉細胞，通常受限於其細胞外基質結構，並沿著主要受力方向平行排列。然而目前大多數體外實驗模型尚無法真實重現體內所經歷之非等向性的力學環境。本研究透過結合微製程技術限制細胞形狀與單軸向拉伸系統，建立精確的幾何與受力控制條件，並驗證外部受力方向為決定細胞骨架重組與下游訊號傳遞的重要開關。我們證實幹細胞內細胞骨架排列方式與機械負載的方向一致時，可促進活化的YAP蛋白移至細胞核;但當拉伸方向垂直於細胞骨架排列方向時，則未觀察到相同現象。進一步分析細胞骨架在細胞受到機械負載的早期階段的反應顯示，平行拉伸會在60秒內誘導肌動蛋白絲結構重組，包含結構斷裂與隨後修復，此過程受到focal adhesion protein zyxin所調控。此外，由zyxin所調控的肌動蛋白絲結構重組之修復反應受到focal adhesion kinase (FAK)所調控，而此反應進一步活化YAP訊號。有鑑於上述分子在機械刺激過程中所調控的反應具有關鍵作用，本研究結果顯示zyxin、YAP在非等向性機械訊號傳導中扮演重要角色外，且可作為細胞適應性反應(cellular adaptive responses)及維持組織體內平衡(tissue homeostasis)提供新的觀點。內容已於2022年發表在Acta Biomater期刊 | zh_TW |
| dc.description.abstract | Cells in the human body are continuously subjected to anisotropic mechanical deformation arising from tissue architecture and functional demands. For example, tenocytes and muscle cells are constrained by their extracellular matrix and typically align parallel to their principal loading direction. However, most in vitro experimental models fail to recapitulate the anisotropic geometric and mechanical environment experienced in vivo. In this study, we integrated cell pattering with a controllable uniaxial stretching system to establish precise control of cell geometry and force direction. We demonstrate that when cytoskeletal is oriented parallel to the direction of mechanical loading, YAP translocate into the nucleus. In contrast, no comparable nuclear translocation is observed when the stretch is applied perpendicular to cytoskeletal alignment. Further analysis of early cytoskeletal response to mechanical loading revealed that parallel stretching induces actin filament remodeling within 60 seconds, characterized by filament disruption followed by repair. This process is mediated by the focal adhesion protein zyxin. Moreover, zyxin-dependent actin repair is regulated by focal adhesion kinase (FAK), and this signaling cascade subsequently promotes YAP activation. Given the critical roles of these mechanism in anisotropic mechanotransduction, our finding indicates that zyxin and YAP serve as key regulators in anisotropic mechanical signaling. These results provide new insights into cellular adaptive responses and contribute to our understanding of tissue homeostasis under directional mechanical stimulation and was published in Acta Biomater in 2022 | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2026-08-11T16:20:06Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2026-08-11T16:20:06Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iii Content v List of Figure vii Chapter 1 Introduction 1 1.1 Mechanotransduction and tissue homeostasis 1 1.2 Directional mechanobiology 3 1.3 How the cell sense uniaxial mechanical stimulation 4 1.4 Zyxin in mechanotransdution 8 1.5 YAP in focal adhesion-dependent mechanotransdution 9 1.6 Research Design 11 Chapter 2 Material and Methods 15 2.1 Cell culture 15 2.2 Microfabrication and Soft lithograph 15 2.3 Mechanical Stimulation 16 2.4 Real-time bioreactor 18 2.5 Inhibition and RNA interference 21 2.6. Fluorescence labeling and microscopy 21 2.7 Image analysis 22 2.8 Statistical analysis 23 Chapter 3 Results 25 3.1 Mechanical stretch promotes YAP Nuclear Translocation 25 3.2 YAP responds to mechanical stretching in a direction-dependent manner 27 3.3 Anisotropic stress fibers remodeling under short-term uniaxial mechanical stretching 29 3.4 Directional stretch induces actin severing and repair 32 3.5 Actomyosin contractility modulates anisotropic actin remodeling 35 3.6 FAK mediates direction-dependent activation during mechanical stretching 40 3.7 Zyxin-mediated cytoskeletal repair controls YAP mechanotransduction 44 Chapter 4 Discussion 53 Reference 60 | - |
| dc.language.iso | en | - |
| dc.subject | YAP | - |
| dc.subject | 非等向性力學傳遞 | - |
| dc.subject | Zyxin | - |
| dc.subject | FAK | - |
| dc.subject | 單軸向拉伸 | - |
| dc.subject | YAP | - |
| dc.subject | anisotropic mechanotransduction | - |
| dc.subject | Zyxin | - |
| dc.subject | FAK | - |
| dc.subject | uniaxial stretching | - |
| dc.title | Zyxin蛋白與肌動蛋白結構調控非等向性YAP力學傳遞 | zh_TW |
| dc.title | Zyxin and actin structure confer anisotropic YAP mechanotransduction | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 114-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 林耿慧;郭津岑;劉雅雯;郭柏齡 | zh_TW |
| dc.contributor.oralexamcommittee | Keng-hui Lin;Jean-Cheng Kuo;Ya-Wen Liu;Po-Ling Kuo | en |
| dc.subject.keyword | YAP; 非等向性力學傳遞; Zyxin; FAK; 單軸向拉伸 | zh_TW |
| dc.subject.keyword | YAP; anisotropic mechanotransduction; Zyxin; FAK; uniaxial stretching | en |
| dc.relation.page | 75 | - |
| dc.identifier.doi | 10.6342/NTU202602764 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2026-08-04 | - |
| dc.contributor.author-college | 工學院 | - |
| dc.contributor.author-dept | 醫學工程學系 | - |
| dc.date.embargo-lift | N/A | - |
| 顯示於系所單位： | 醫學工程學研究所 | |
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