PDF(Sci-hub)
Abstract：
By combining large-scale dissipative particle dynamics and steered molecular dynamics simulations, we investigate the mechanochemical cellular internalization pathways of homogeneous and heterogeneous nanohydrogels and demonstrate that membrane internalization is determined by the crosslink density and encapsulation ability of nanohydrogels. The homogeneous nanohydrogels with a high crosslink density and low encapsulation ability behave as soft nanoparticles partially wrapped by the membrane, while those with a low crosslink density and high encapsulation ability permeate into the membrane. Regardless of the crosslink density, the homogeneous nanohydrogels undergo typical dual morphological deformations. The local lipid nanodomains are identified at the contacting region between the membrane and nanohydrogels because of different diffusion behaviors between lipid and receptor molecules during the internalization process. The yolk@shell heterogeneous nanohydrogels present a different mechanochemical cellular internalization pathway. The yolk with strong affinity is directly in contact with the membrane, resulting in partial membrane wrapping, and the contacting area is much reduced when compared to homogenous nanohydrogels, leading to a smaller lipid nanodomain and thus avoiding related cellular toxicity. Our findings provide a critical mechanism understanding of the biological pathways of nanohydrogels and may guide the molecular design of the hydrogel-based materials for controlled release drug delivery, tissue engineering, and cell culture.
摘要：
通过结合大规模耗散粒子动力学和转向分子动力学模拟，我们研究了均相和非均相纳米水凝胶的机械化学细胞内化途径，并证明了膜内化是由纳米水凝胶的交联密度和包封能力决定的。具有高交联密度和低包封能力的均质纳米水凝胶表现为部分被膜包裹的软纳米颗粒。而那些具有低交联密度和高封装能力的渗透进入膜。无论交联密度如何，均匀的纳米水凝胶经历典型的双重形态变形。由于内化过程中脂质和受体分子之间的扩散行为不同，因此在膜和纳米水凝胶之间的接触区域鉴定了局部脂质纳米结构域。蛋黄@壳异质纳米水凝胶呈现不同的机械化学细胞内化途径。亲和力强的蛋黄直接与膜接触，导致部分膜包裹，与均质纳米水凝胶相比，接触面积大大减少，导致更小的脂质纳米结构域，从而避免相关的细胞毒性。我们的发现为纳米水凝胶的生物学途径提供了关键的机制理解，并可能指导用于控释药物递送的基于水凝胶的材料的分子设计。组织工程,和细胞培养。
