标题： 差分交联和收缩马达驱动核染色质压缩 显示英文标题

标题： Differential Crosslinking and Contractile Motors Drive Nuclear Chromatin Compaction

摘要： 在间期，典型的细胞核具有转录活跃的常染色质和被抑制的异染色质区域的空间分隔。 在传统的核组织中，常染色质主要占据核的内部，而异染色质的密度大约比常染色质高50%，并位于核的外围附近。 外围染色质的组织还可以通过核纤层进一步调节，而核纤层本身是一种可变形的结构。 虽然已经探索了刚性核内分隔的多种生物物理机制，但我们研究了一个由与可变形的聚合物核纤层壳层相连的活性交联聚合物组成的染色质模型。 收缩马达、壳层的可变形性以及交联的空间分布都在这种分隔中起着关键作用。 我们发现，径向交联密度分布，即使在核的边缘仅有较小的线性差异的较高交联密度，结合收缩马达活动，会驱动基因组分离，这与实验观察结果一致。 这是由于收缩马达优先将交联拉入核的外围附近，形成高密度区域，从而促进异染色质的形成。 我们还发现，在核纤层壳层下方的异染色质优先压缩的情况下，核皱褶的刚度增加，这与施加纳米压痕时核的即时硬化一致。 我们以我们的模型预测的实验验证潜力作为结论。 显示英文摘要

摘要： During interphase, a typical cell nucleus features spatial compartmentalization of transcriptionally active euchromatin and repressed heterochromatin domains. In conventional nuclear organization, euchromatin predominantly occupies the nuclear interior, while heterochromatin, which is approximately 50% more dense than euchromatin, is positioned near the nuclear periphery. Peripheral chromatin organization can be further modulated by the nuclear lamina, which is itself a deformable structure. While a number of biophysical mechanisms for compartmentalization within rigid nuclei have been explored, we study a chromatin model consisting of an active, crosslinked polymer tethered to a deformable, polymeric lamina shell. Contractile motors, the deformability of the shell, and the spatial distribution of crosslinks all play pivotal roles in this compartmentalization. We find that a radial crosslink density distribution, even with a small linear differential of higher crosslinking density at the edge of the nucleus, combined with contractile motor activity, drives genomic segregation, in agreement with experimental observations. This arises from contractile motors preferentially drawing crosslinks into their vicinity at the nuclear periphery, forming high-density domains that promote heterochromatin formation. We also find an increased stiffness of nuclear wrinkles given the preferential heterochromatin compaction below the lamina shell, which is consistent with instantaneous nuclear stiffening under applied nanoindentation. We conclude with the potential for experimental validation of our model predictions.