Cantrall Gregory R, Chauhan Gaurav, Abel Steven M
Department of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville.
bioRxiv. 2025 Sep 6:2025.09.04.674235. doi: 10.1101/2025.09.04.674235.
Macromolecular crowding can significantly impact the behavior of biopolymers, with crowding-induced depletion interactions influencing both the conformations and surface adsorption of individual polymers. Although previous studies have explored the influence of homogeneous polymer stiffness in crowded conditions, biomolecules such as DNA can exhibit sequence-dependent stiffness, and DNA origami nanoparticles can be designed with alternating stiff and flexible domains. In this work, we use Langevin dynamics simulations to characterize how nonuniform bending stiffness modulates the conformations and adsorption of polymers in crowded environments. By systematically varying the relative length and arrangement of flexible and semiflexible domains along a linear chain, we show that increasing osmotic pressure leads to a pattern-dependent collapse of the polymer, as revealed by a decrease in the radius of gyration. In general, large flexible regions promote polymer collapse, although flexible domains separating extended semiflexible regions can facilitate their contact, leading to stable folded conformations. When a surface is present, large semiflexible domains promote adsorption, and the pattern of stiffness can be used to control the adsorption threshold. Our findings provide insight into the impact of spatially varying stiffness on the behavior of polymers in crowded environments, highlighting mechanisms relevant to biopolymers and deformable nanoparticles in both cellular and cell-free contexts.
大分子拥挤效应会显著影响生物聚合物的行为，拥挤诱导的耗尽相互作用会影响单个聚合物的构象和表面吸附。尽管先前的研究已经探讨了在拥挤条件下均匀聚合物刚度的影响，但像DNA这样的生物分子可以表现出序列依赖性刚度，并且可以设计具有交替刚性和柔性结构域的DNA折纸纳米颗粒。在这项工作中，我们使用朗之万动力学模拟来表征非均匀弯曲刚度如何调节聚合物在拥挤环境中的构象和吸附。通过系统地改变柔性和半柔性结构域沿线性链的相对长度和排列，我们表明，随着渗透压的增加，聚合物会出现依赖于模式的塌缩，这通过回转半径的减小得以揭示。一般来说，大的柔性区域会促进聚合物塌缩，尽管分隔延伸半柔性区域的柔性结构域可以促进它们的接触，从而形成稳定的折叠构象。当存在表面时，大的半柔性结构域会促进吸附，并且刚度模式可用于控制吸附阈值。我们的研究结果深入了解了空间变化的刚度对聚合物在拥挤环境中行为的影响，突出了与细胞内和无细胞环境中的生物聚合物和可变形纳米颗粒相关的机制。
