As an important intracellular genetic and regulatory center, the nucleus is not only a terminal effector of intracellular biochemical signals, but also has a significant impact on cell function and phenotype through direct or indirect regulation of nuclear mechanistic cues after the cell senses and responds to mechanical stimuli. The nucleus relies on chromatin-nuclear membrane-cytoskeleton infrastructure to couple signal transduction, and responds to these mechanical stimuli in the intracellular and extracellular physical microenvironments. Changes in the morphological structure of the nucleus are the most intuitive manifestation of this mechanical response cascades and are the basis for the direct response of the nucleus to mechanical stimuli. Based on such relationships of the nucleus with cell behavior and phenotype, abnormal nuclear morphological changes are widely used in clinical practice as disease diagnostic tools. This review article highlights the latest advances in how nuclear morphology responds and adapts to mechanical stimuli. Additionally, this article will shed light on the factors that mechanically regulate nuclear morphology as well as the tumor physio-pathological processes involved in nuclear morphology and the underlying mechanobiological mechanisms. It provides new insights into the mechanisms that nuclear mechanics regulates disease development and its use as a potential target for diagnosis and treatment.
细胞核作为细胞内重要的遗传与调控中心,不但是细胞内生化信号的终端效应器,还能在细胞感知并应答力学刺激后,通过直接或间接的核力学信号调节对细胞的功能与表型产生重要影响。细胞核依靠染色质—核膜—细胞骨架等基础结构将其与其他胞内、外的物理微环境耦合,响应力学刺激并做出应答。该力学响应级联中,细胞核形态结构的变化是最直观的表现,也是细胞核直接响应力学刺激的基础。基于此类细胞核与细胞行为、表型的联系,核的异常形态变化被作为疾病诊断工具广泛用于临床实践。本文回顾了细胞核形变如何响应和适应力学刺激的证据,并着重综述了细胞核形变的力学调控因素,以及核形变涉及到的包括肿瘤在内的生理病理过程及其力学调控机制和研究进展,为深入理解细胞核力学参与的疾病发展调控机制和作为潜在靶点用于诊疗提供新的思路。.
Keywords: Chromatin reconstitution; Cytoskeletal mechanics; Nuclear deformation; Nuclear mechanotransduction; Tumor.