Department of Physics and Astronomy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Biology Department, The University of Massachusetts at Amherst, Amherst, MA 01003, USA.
Cells. 2020 Jul 6;9(7):1623. doi: 10.3390/cells9071623.
Cell nuclei are paramount for both cellular function and mechanical stability. These two roles of nuclei are intertwined as altered mechanical properties of nuclei are associated with altered cell behavior and disease. To further understand the mechanical properties of cell nuclei and guide future experiments, many investigators have turned to mechanical modeling. Here, we provide a comprehensive review of mechanical modeling of cell nuclei with an emphasis on the role of the nuclear lamina in hopes of spurring future growth of this field. The goal of this review is to provide an introduction to mechanical modeling techniques, highlight current applications to nuclear mechanics, and give insight into future directions of mechanical modeling. There are three main classes of mechanical models-schematic, continuum mechanics, and molecular dynamics-which provide unique advantages and limitations. Current experimental understanding of the roles of the cytoskeleton, the nuclear lamina, and the chromatin in nuclear mechanics provide the basis for how each component is subsequently treated in mechanical models. Modeling allows us to interpret assay-specific experimental results for key parameters and quantitatively predict emergent behaviors. This is specifically powerful when emergent phenomena, such as lamin-based strain stiffening, can be deduced from complimentary experimental techniques. Modeling differences in force application, geometry, or composition can additionally clarify seemingly conflicting experimental results. Using these approaches, mechanical models have informed our understanding of relevant biological processes such as migration, nuclear blebbing, nuclear rupture, and cell spreading and detachment. There remain many aspects of nuclear mechanics for which additional mechanical modeling could provide immediate insight. Although mechanical modeling of cell nuclei has been employed for over a decade, there are still relatively few models for any given biological phenomenon. This implies that an influx of research into this realm of the field has the potential to dramatically shape both future experiments and our current understanding of nuclear mechanics, function, and disease.
细胞核对于细胞功能和机械稳定性都至关重要。细胞核的这两个作用是相互交织的，因为细胞核机械性质的改变与细胞行为和疾病的改变有关。为了进一步了解细胞核的机械性质，并指导未来的实验，许多研究人员转向机械建模。在这里，我们提供了一个对细胞核机械建模的全面综述，重点介绍核层在其中的作用，希望能推动该领域的进一步发展。本综述的目的是介绍机械建模技术，突出当前在核力学中的应用，并深入了解机械建模的未来方向。有三种主要的机械模型——示意图、连续介质力学和分子动力学——它们提供了独特的优势和局限性。目前对细胞骨架、核层和染色质在核力学中的作用的实验理解为如何在机械模型中处理每个组件提供了基础。建模允许我们解释特定实验的关键参数的结果，并对涌现行为进行定量预测。当可以从互补的实验技术推断出基于层的应变硬化等涌现现象时，这尤其强大。建模在力的应用、几何形状或组成上的差异还可以澄清看似矛盾的实验结果。通过这些方法，机械模型使我们能够深入了解相关的生物学过程，如迁移、核泡状化、核破裂以及细胞扩展和脱离。仍然有许多核力学方面的问题需要额外的机械建模来提供直接的见解。尽管细胞核的机械建模已经使用了十多年，但对于任何给定的生物学现象，仍然相对较少的模型。这意味着，在这一领域投入更多的研究可能会对未来的实验和我们当前对核力学、功能和疾病的理解产生重大影响。
