2020-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/658263於動脈和肌腱等緻密的結締組織中，膠原和彈性蛋白等基質形成平行波狀纖維束，此結構提供組織具彈性又可抵抗過載之機械功能；生長於這種結構中的細胞遵循相同的型態並呈現細長且波狀的細胞核。受傷和老化會破壞此基質與細胞結構，導致組織功能受損和發炎。我們之前開發了2D和3D材料平台重建這種結構，發現細胞及其細胞核不僅遵循此波狀結構，且增加膠原蛋白轉錄與分泌。本計畫假設波狀細胞會活化其Rac1蛋白，因此調節細胞核形態和骨架結構，從而控制膠原蛋白轉錄。通過結合微製程與螢光生物探針，本計畫研究波狀細胞中的結構和轉錄控制機制，並了解機械信號如何影響膠原蛋白表現。該項目的結果將有利於結構對轉錄調控之機轉，以及生物材料設計與減少老化和受損組織中病態結構的策略。 In dense regular connective tissues such as arteries and tendons, matrix proteins including collagen and elastin are organized into parallel and wavy fiber bundles. This structure provides mechanical functionality of the tissue where it is flexible yet resists overloading. Cells embedded in these structures follow the same organization and exhibit elongated and wavy nuclei. Injury and aging disrupt the matrix and cellular structures, leading to impaired tissue functionality and inflammatory cytokine release. We developed both 2D and 3D material platforms to recreate this structure and found that cells, and their nuclei, not only follow the wavy structure, they also have increased phenotypic expressions. In this proposal, we hypothesize that localized Rac1 activation regulates nuclear morphology and organization in the wavy cells, thus controlling the phenotypic transcriptions. By combining microfabrication and fluorescent biosensors, the current project proposes to investigate the structural and transcriptional control mechanisms in the wavy cells and examine how mechanical cues impact the crosstalk between mechano-sensing and collagen expression regulation pathways. Findings from this project would greatly benefit efforts in structural transcription regulation, future biomaterial designs, and strategies to minimize the effects of aberrant scar formation in aging and injured tissues.力生物學細胞核細胞骨架RacRhoGTPase膠原蛋白MechanotransductionNucleusCytoskeletoncollagen