Robust antigen-specific tuning of the nanoscale barrier properties of biogels using matrix-associating IgG and IgM antibodies
Robust antigen-specific tuning of the nanoscale barrier properties of biogels using matrix-associating IgG and IgM antibodies
复制标题
使用基质相关 IgG 和 IgM 抗体对生物凝胶的纳米级屏障特性进行稳健的抗原特异性调节
DOI：
10.1016/j.actbio.2019.03.023
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发表时间：
2019
影响因子：
9.7
通讯作者：
Lai, Samuel K.
中科院分区：
文献类型：
--
作者：
Schiller, Jennifer L.;Marvin, Allison;McCallen, Justin D.;Lai, Samuel K.
生物水凝胶是一种选择性屏障，它限制有害物质的通过，但允许营养物质和选择细胞的快速移动。目前的方法，以调节的屏障性能的凝胶通常涉及体积变化，以限制扩散的空间位阻或直接高亲和力的相互作用与微观结构的成分。在这里，我们介绍了第三种机制，基于抗体为基础的第三方锚定，结合特定的外来物种，但只形成弱和短暂的债券与生物素成分。对生物素凝胶组分的弱亲和力允许抗体锚定物快速积累在特定外来物质的表面上，并通过与生物素凝胶基质的多重交联促进固定。使用基底膜Matrigel®和层粘连蛋白/巢蛋白的混合物，我们证明了抗原特异性IgG和IgM（但不是对照）有效地包裹各种单独的纳米颗粒。将鼠伤寒沙门氏菌结合IgG添加到琼脂糖凝胶中显著降低了这些高度运动的细菌的侵袭。这些结果强调了一种通用的策略，通过该策略，生物水凝胶的阻隔性能可以很容易地与针对不同阵列的particulate.Statement的分子特异性进行调整生物水凝胶（Biological Hydrogel，Biogeles）在生命系统中是必不可少的，以控制细胞和有害物质的运动。然而，目前控制凝胶内传输的方法依赖于在总体水平上改变凝胶基质的微观结构，或者通过减小孔径以限制通过空间位阻的通道，或者通过化学改性基质本身。这两种方法要么是非特异性的，要么是不可扩展的。在这里，我们提供了一种新的方法，基于弱粘性的第三方分子锚，允许各种外来实体被困在一个凝胶内，同时具有特殊的效力和分子特异性，而不会干扰凝胶的整体性质。这一策略大大提高了我们在纳米级控制凝胶特性的能力，包括那些用于伤口愈合或组织工程应用的凝胶。
Biological hydrogels (biogels) are selective barriers that restrict passage of harmful substances yet allow the rapid movement of nutrients and select cells. Current methods to modulate the barrier properties of biogels typically involve bulk changes in order to restrict diffusion by either steric hindrance or direct high-affinity interactions with microstructural constituents. Here, we introduce a third mechanism, based on antibody-based third party anchors that bind specific foreign species but form only weak and transient bonds with biogel constituents. The weak affinity to biogel constituents allows antibody anchors to quickly accumulate on the surface of specific foreign species and facilitates immobilization via multiple crosslinks with the biogel matrix. Using the basement membrane Matrigel® and a mixture of laminin/entactin, we demonstrate that antigen-specific, but not control, IgG and IgM efficiently immobilize a variety of individual nanoparticles. The addition ofSalmonella typhimurium-binding IgG to biogel markedly reduced the invasion of these highly motile bacteria. These results underscore a generalized strategy through which the barrier properties of biogels can be readily tuned with molecular specificity against a diverse array of particulates.Statement of SignificanceBiological hydrogels (biogels) are essential in living systems to control the movement of cells and unwanted substances. However, current methods to control transport within biogels rely on altering the microstructure of the biogel matrix at a gross level, either by reducing the pore size to restrict passage through steric hindrance or by chemically modifying the matrix itself. Both methods are either nonspecific or not scalable. Here, we offer a new approach, based on weakly adhesive third-party molecular anchors, that allow for a variety of foreign entities to be trapped within a biogel simultaneously with exceptional potency and molecular specificity, without perturbing the bulk properties of the biogel. This strategy greatly increases our ability to control the properties of biogels at the nanoscale, including those used for wound healing or tissue engineering applications.