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Reversible coating of cells with synthetic polymers for mechanochemical regulation of cell adhesion
bioRxiv - Biophysics Pub Date : 2020-10-26 , DOI: 10.1101/2020.10.25.354480
Yoshihisa Kaizuka , Rika Machida

The chemical control of cell-cell interactions using synthetic materials is useful for a wide range of biomedical applications. Herein, we report a method to regulate cell adhesion and dispersion by introducing repulsive forces to live cell membranes. To induce repulsion, we tethered amphiphilic polymers, such as cholesterol-modified polyethylene glycol (PEG-CLS) to cell membranes. These amphiphilic polymers both bind to and dissociate rapidly from membranes and thus, enable the reversible coating of cells by mixing and washout without requiring genetic manipulation or chemical synthesis in the cells. We found that the repulsive forces introduced by these tethered polymers can induce cell detachment from a substrate and allow cell dispersion in a suspension, modulate the speed of cell migration, and improve the separation of cells from tissues. Our analyses showed that coating the cells with tethered polymers most likely generated two distinct repulsive forces, lateral tension and steric repulsion, on the surface, which can be tuned by altering the polymer size and density. We also modeled how these two forces can be generated in kinetically distinctive manners to explain the various responses of cells to the coating. Collectively, our observations and analyses show how we can mechanochemically regulate cell adhesion and dispersion and may contribute to the optimization of chemical coating strategies for regulating various types of cell-cell interacting systems.

中文翻译:

用合成聚合物可逆涂覆细胞,以机械化学方式调节细胞粘附

使用合成材料对细胞间相互作用进行化学控制可用于多种生物医学应用。在本文中,我们报告了一种通过向活细胞膜引入排斥力来调节细胞粘附和分散的方法。为了诱导排斥,我们将两亲性聚合物(例如胆固醇改性的聚乙二醇(PEG-CLS))拴在细胞膜上。这些两亲性聚合物都与膜结合并快速从膜上解离,因此,通过混合和冲洗可以使细胞可逆地被覆,而无需细胞中的基因操作或化学合成。我们发现,由这些束缚的聚合物引入的排斥力可以诱导细胞与基质分离,并使细胞分散在悬浮液中,调节细胞迁移的速度,并改善细胞与组织的分离。我们的分析表明,用束缚的聚合物覆盖细胞最有可能在表面上产生两个不同的排斥力,即横向张力和空间排斥力,可以通过改变聚合物的大小和密度进行调整。我们还对如何以动力学上独特的方式生成这两个力进行建模,以解释细胞对涂层的各种响应。总的来说,我们的观察和分析表明我们如何机械化学调节细胞粘附和分散,并可能有助于优化化学涂层策略以调节各种类型的细胞-细胞相互作用系统。我们还对如何以动力学上独特的方式生成这两个力进行建模,以解释细胞对涂层的各种响应。总的来说,我们的观察和分析表明我们如何机械化学调节细胞粘附和分散,并可能有助于优化化学涂层策略以调节各种类型的细胞-细胞相互作用系统。我们还对如何以动力学上独特的方式生成这两个力进行建模,以解释细胞对涂层的各种响应。总的来说,我们的观察和分析表明我们如何机械化学调节细胞粘附和分散,并可能有助于优化化学涂层策略以调节各种类型的细胞-细胞相互作用系统。
更新日期:2020-10-26
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