Antibody-mediated trapping in biological hydrogels is governed by sugar-sugar hydrogen bonds.,Acta Biomaterialia

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Antibody-mediated trapping in biological hydrogels is governed by sugar-sugar hydrogen bonds.
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-03-05 , DOI: 10.1016/j.actbio.2020.03.002
Jennifer L Schiller ₁ , Mary M Fogle ₁ , Olivia Bussey ₁ , William J Kissner ₂ , David B Hill ₃ , Samuel K Lai ₄

Affiliation

N-glycans on IgG and IgM antibodies (Ab) facilitate Ab-mediated crosslinking of viruses and nanoparticles to the major structural elements of mucus and basement membranes. Nevertheless, the chemical moieties in these biological hydrogel matrices to which Ab can bind remain poorly understood. To gain insights into the chemistries that support Ab-matrix interactions, we systematically evaluated IgG- and IgM-mediated trapping of nanoparticles in different polysaccharide-based biogels with unique chemical features. In agarose, composed of alternating d-galactose and 3,6-anhydro-l-galactopyranose (i.e. hydroxyl groups only), anti-PEG IgM but not anti-PEG IgG trapped PEGylated nanoparticles. In alginate, comprised of homopolymeric blocks of mannuronate and guluronate (i.e. both hydroxyl and carboxyl groups), both IgG and IgM trapped PEGylated nanoparticles. In contrast, chitosan, comprised primarily of glucosamine (i.e. both hydroxyl and primary amine groups), did not facilitate either IgG- or IgM-mediated trapping. IgG-mediated trapping in alginate was abrogated upon removal of IgG N-glycans, whereas IgM-mediated trapping was eliminated in agarose but not alginate upon desialylation. These results led us to propose a model in which hydrogen bonding between carboxyl and hydroxyl groups of glycans on both Ab and matrix facilitates Ab-mediated trapping of pathogens in biogels. Our work here offers a blueprint for designing de novo hydrogels that could harness Ab-matrix interactions for various biomedical and biological applications. STATEMENT OF SIGNIFICANCE: Here, we interrogated the molecular mechanism of antibody-mediated trapping to address what are the chemical moieties on biogels that are essential for facilitating trapping in biogels. We systematically evaluated the potencies of IgG and IgM to trap nanoparticles in different polysaccharide-based biogels with unique and highly defined chemical moieties: hydroxyl groups (agarose), amine groups (chitosan), and carboxyl groups (alginate). We discovered that only hydroxyl/carboxyl hydrogen bonds (and stronger) are sufficiently strong enough to facilitate antibody-mediated trapping; weaker hydroxyl/hydroxyl bonds or hydroxyl/amine bonds fail to adequately slow particles. Our findings presents the first blueprint for how to engineer de novo biogels that are capable of harnessing antibodies to immobilize foreign entities in the biogels, for applications ranging from infectious disease to contraception to purification processes.

中文翻译：

生物水凝胶中抗体介导的捕获受糖-糖氢键控制。

IgG 和 IgM 抗体 (Ab) 上的 N-聚糖促进 Ab 介导的病毒和纳米颗粒与粘液和基底膜的主要结构元素的交联。然而，Ab 可以结合的这些生物水凝胶基质中的化学部分仍然知之甚少。为了深入了解支持 Ab-基质相互作用的化学物质，我们系统地评估了 IgG 和 IgM 介导的纳米粒子在具有独特化学特征的不同多糖生物凝胶中的捕获。在琼脂糖中，由交替的 d-半乳糖和 3,6-脱水-l-吡喃半乳糖（即仅羟基）组成，抗 PEG IgM 而不是抗 PEG IgG 捕获 PEG 化的纳米颗粒。在藻酸盐中，由甘露糖醛酸盐和古洛糖醛酸盐的均聚嵌段（即羟基和羧基）组成，IgG 和 IgM 都捕获了聚乙二醇化的纳米颗粒。相反，主要由葡糖胺（即羟基和伯胺基团）组成的壳聚糖不促进IgG-或IgM-介导的捕获。藻酸盐中 IgG 介导的捕获在去除 IgG N-聚糖后被消除，而 IgM 介导的捕获在琼脂糖中被消除，但在脱唾液酸化后藻酸盐中没有。这些结果使我们提出了一个模型，其中 Ab 和基质上聚糖的羧基和羟基之间的氢键有助于 Ab 介导的病原体在生物凝胶中的捕获。我们在这里的工作为设计从头水凝胶提供了蓝图，该水凝胶可以利用 Ab-matrix 相互作用进行各种生物医学和生物学应用。意义声明：在这里，我们研究了抗体介导的捕获的分子机制，以解决生物凝胶上哪些化学部分对于促进生物凝胶中的捕获至关重要。我们系统地评估了 IgG 和 IgM 将纳米粒子捕获在不同的基于多糖的生物凝胶中的能力，这些生物凝胶具有独特且高度明确的化学部分：羟基（琼脂糖）、胺基（壳聚糖）和羧基（海藻酸盐）。我们发现只有羟基/羧基氢键（和更强的）足够强，足以促进抗体介导的捕获。较弱的羟基/羟基键或羟基/胺键不能充分减慢粒子。我们的研究结果展示了如何设计能够利用抗体将外来实体固定在生物凝胶中的从头生物凝胶的第一个蓝图，

更新日期：2020-03-05

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