Athirasala Avathamsa, Hirsch Nivi, Buxboim Amnon
Alexander Grass Center for Bioengineering, School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
Curr Opin Cell Biol. 2017 Jun;46:119-127. doi: 10.1016/j.ceb.2017.04.004. Epub 2017 Jun 20.
The cell nucleus is a hallmark of eukaryotic evolution, where gene expression is regulated and the genome is replicated and repaired. Yet, in addition to complex molecular processes, the nucleus has also evolved to serve physical tasks that utilize its optical and mechanical properties. Nuclear mechanotransduction of externally applied forces and extracellular stiffness is facilitated by the physical connectivity of the extracellular environment, the cytoskeleton and the nucleoskeletal matrix of lamins and chromatin. Nuclear mechanosensor elements convert applied tension into biochemical cues that activate downstream signal transduction pathways. Mechanoregulatory networks stabilize a contractile cell state with feedback to matrix, cell adhesions and cytoskeletal elements. Recent advances have thus provided mechanistic insights into how forces are sensed from within, that is, in the nucleus where cell-fate decision-making is performed.
细胞核是真核生物进化的标志,基因表达在此受到调控,基因组在此进行复制和修复。然而,除了复杂的分子过程外,细胞核还进化出了利用其光学和机械特性来执行物理任务的功能。细胞外环境、细胞骨架以及由核纤层蛋白和染色质组成的核骨架基质之间的物理连接,促进了外力和细胞外硬度的核机械转导。核机械传感元件将施加的张力转化为生化信号,从而激活下游信号转导通路。机械调节网络通过对基质、细胞黏附以及细胞骨架元件的反馈,稳定收缩性细胞状态。因此,最近的进展为从细胞内部(即进行细胞命运决定的细胞核)感知力的机制提供了深入见解。