Department of Science and Technology of Materials and Fluids, Fluid Dynamics Technology Group (TFD), Aragon Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain.
Department of Mechanical Engineering, Multiscale in Mechanical and Biological Engineering (M2BE), Aragon Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain.
Biophys J. 2024 Oct 1;123(19):3386-3396. doi: 10.1016/j.bpj.2024.08.003. Epub 2024 Aug 8.
The nucleus of eukaryotic cells is constantly subjected to different kinds of mechanical stimuli, which can impact the organization of chromatin and, subsequently, the expression of genetic information. Experiments from different groups showed that nuclear deformation can lead to transient or permanent condensation or decondensation of chromatin and the mechanical activation of genes, thus altering the transcription of proteins. Changes in chromatin organization, in turn, change the mechanical properties of the nucleus, possibly leading to an auxetic behavior. Here, we model the mechanics of the nucleus as a chemically active polymer gel in which the chromatin can exist in two states: a self-attractive state representing the heterochromatin and a repulsive state representing euchromatin. The model predicts reversible or irreversible changes in chromatin condensation levels upon external deformations of the nucleus. We find an auxetic response for a broad range of parameters under small and large deformations. These results agree with experimental observations and highlight the key role of chromatin organization in the mechanical response of the nucleus.
真核细胞的核体会不断受到不同种类的机械刺激，这些刺激会影响染色质的组织，进而影响遗传信息的表达。来自不同研究小组的实验表明，核变形会导致染色质的瞬时或永久凝聚或去凝聚，以及基因的机械激活，从而改变蛋白质的转录。染色质组织的变化反过来又会改变核的力学性质，可能导致超弹性行为。在这里，我们将核的力学模型化为一种化学活性聚合物凝胶，其中染色质可以存在于两种状态：代表异染色质的自吸引状态和代表常染色质的排斥状态。该模型预测了核的外部变形会导致染色质凝聚水平的可逆或不可逆变化。我们发现，在小变形和大变形下，染色质凝聚水平会发生超弹性响应。这些结果与实验观察结果一致，并强调了染色质组织在核的力学响应中的关键作用。
