波浪狀細胞藉肌動蛋白結構調控細胞核型態

Abstract

人體中許多組織具有平行波浪狀結構的膠原蛋白纖維，這種結構中的細胞以及細胞核也具有波浪狀的型態，我們之前的研究發現波浪結構可控制細胞的基因表現，且前人研究也指出細胞核型態可調控基因表現。然而目前還未瞭解控制細胞核形狀的機制。為探討不同曲率如何影響細胞與細胞核，我們利用微壓印(micro-contact printing)製作直線及不同彎度的PDMS 基質並種上間質幹細胞。細胞與細胞核的確會隨著各式結構生長，我們並進一步推論細胞型態是經由細胞骨架調控細胞核型態。細胞骨架的抑制結果顯示失去肌動蛋白將使細胞核曲率提升，而不同位置的肌動蛋白次結構將導致細胞核有不同的形變。在肌動蛋白的抑制過程中，肌動蛋白團(actin cluster)一旦發生，將導致細胞核被壓迫彎曲，而細胞核的可塑性質會記憶這個彎曲。細胞貼附基質時，肌動蛋白骨架將隨細胞型態形成並改變細胞核型態，因此細胞核的形狀與肌動蛋白有關。未來將調查肌動蛋白次結構與LINC對細胞核形變與細胞行為表現。

Many tissues are composed of aligned collagen fibers in the body, the cell and nucleus in this structure exhibit wavy morphology. Our study, along with previous studies, show that wavy structures control cell gene expression and nuclear morphology may regulate gene expression. To investigate how wavy structure affect cell and nucleus, we used micro-contact printing to fabricate PDMS microgroove substrates with straight and wavy structures and then seeded human mesenchymal stem cells (MSCs) on the patterns. Cells and nuclei conformed to different pattern shapes, we further infer that nuclear morphology is regulated by cell cytoskeleton. The results of cytoskeleton inhibition show that without actin fibers the nuclear curvature increased, and actin substructures could lead to different nuclear deformation. Actin inhibition or disruption generates actin fragments, termed actin clusters here, which deforms the malleable nucleus. During cell adhesion and spreading, the developing actin cytoskeleton would control nucleus depending on cell morphology. These results indicate the actin controls nuclear morphology. Future study would be exploring contributions to nuclear deformation and cell phenotype by actin substructures and LINC complex.