Mechanobiology Institute & Department of Biological Sciences, National University of Singapore, Singapore.
Annu Rev Biophys. 2011;40:361-78. doi: 10.1146/annurev-biophys-042910-155319.
Cells integrate physicochemical signals on the nanoscale from the local microenvironment, resulting in altered functional nuclear landscape and gene expression. These alterations regulate diverse biological processes including stem cell differentiation, establishing robust developmental genetic programs and cellular homeostatic control systems. The mechanisms by which these signals are integrated into the 3D spatiotemporal organization of the cell nucleus to elicit differential gene expression programs are poorly understood. In this review I analyze our current understanding of mechanosignal transduction mechanisms to the cell nucleus to induce differential gene regulation. A description of both physical and chemical coupling, resulting in a prestressed nuclear organization, is emphasized. I also highlight the importance of spatial dimension in chromosome assembly, as well as the temporal filtering and stochastic processes at gene promoters that may be important in understanding the biophysical design principles underlying mechanoregulation of gene transcription.
细胞整合来自局部微环境的纳米尺度的物理化学信号，导致功能核景观和基因表达的改变。这些改变调节多种生物过程，包括干细胞分化、建立稳健的发育遗传程序和细胞内稳态控制系统。这些信号如何整合到细胞核的三维时空组织中，从而引发不同的基因表达程序，目前还知之甚少。在这篇综述中，我分析了我们目前对机械信号转导机制到细胞核以诱导差异基因调控的理解。强调了物理和化学耦合导致的预加应力核组织的描述。我还强调了空间维度在染色体组装中的重要性，以及基因启动子处的时空过滤和随机过程，这对于理解机械调节基因转录的生物物理设计原则可能很重要。
