非等向性YAP力學傳遞

Abstract

細胞在天然環境下有許多不同的型態，因為這些型態的不同，細胞內骨架結構也會有所不同。在生理運動下，這些細胞時常感受到非等向性的力學刺激。研究文獻指出非等向性的力學刺激會造成細胞骨架、focal adhesion及基因表現因受力方向的不同而有所差異。YAP是會受力學刺激影響的轉錄輔助活化因子，當它活化時會易位至細胞核。我們假設非等向性的力學刺激會造成YAP有不同的反應，進而導致不同的基因表現。因此，利用微壓印技術使細胞長成橢圓及直線等不同形狀，並施以單軸向的拉伸來探討YAP的非等向性反應。我們發現YAP在直線平行拉伸的細胞才會易位至細胞核。此外，結果指出YAP的非等向性力學傳遞是由細胞形狀、肌凝蛋白及zyxin蛋白所調節。這提供我們一個新的觀點去進一步研究zyxin蛋白和肌凝蛋白在非等向性YAP力學傳遞中的關係。

Cells in their native environment have various morphologies, which are reflected in cytoskeletal structures. In addition, due to physiological tissue movements, mechanical strains applied to cells are often anisotropic. Studies have shown that anisotropic loading change cytoskeleton architecture, focal adhesion organization, and gene expression. YAP is a mechano-response transcriptional coactivator that translocates to the nucleus when activated. We hypothesize that anisotropic mechanical loading results in a direction-dependent YAP response, which may contribute to morphology-dependent gene expression changes. Microcontact printed cells in capsular and linear patterns were subjected to the uniaxial cyclic stretch. We found YAP nuclear translocation only occurred in parallelly stretched linear cells. Furthermore, our results indicated that cell shape, myosin Ⅱ, and zyxin regulate the anisotropic YAP mechanosensing. Our study provides new insights to study the relationship between zyxin and myosin in anisotropic YAP mechanotransduction.