Newby Jay, Schiller Jennifer L, Wessler Timothy, Edelstein Jasmine, Forest M Gregory, Lai Samuel K
Department of Mathematics, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599, USA.
Department of Applied Physical Sciences, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599, USA.
Nat Commun. 2017 Oct 10;8(1):833. doi: 10.1038/s41467-017-00739-6.
Biopolymeric matrices can impede transport of nanoparticulates and pathogens by entropic or direct adhesive interactions, or by harnessing "third-party" molecular anchors to crosslink nanoparticulates to matrix constituents. The trapping potency of anchors is dictated by association rates and affinities to both nanoparticulates and matrix; the popular dogma is that long-lived, high-affinity bonds to both species facilitate optimal trapping. Here we present a contrasting paradigm combining experimental evidence (using IgG antibodies and Matrigel®), a theoretical framework (based on multiple timescale analysis), and computational modeling. Anchors that bind and unbind rapidly from matrix accumulate on nanoparticulates much more quickly than anchors that form high-affinity, long-lived bonds with matrix, leading to markedly greater trapping potency of multiple invading species without saturating matrix trapping capacity. Our results provide a blueprint for engineering molecular anchors with finely tuned affinities to effectively enhance the barrier properties of biogels against diverse nanoparticulate species.Biological polymeric matrices often use molecular anchors, such as antibodies, to trap nanoparticulates. Here, the authors find that anchor-matrix bonds that are weak and short-lived confer superior trapping potency, contrary to the prevailing belief that effective molecular anchors should form strong bonds to both the matrix and the nanoparticulates.
生物聚合物基质可通过熵相互作用或直接粘附相互作用，或利用“第三方”分子锚将纳米颗粒交联到基质成分上，从而阻碍纳米颗粒和病原体的运输。分子锚的捕获能力取决于其与纳米颗粒和基质的结合速率及亲和力；普遍的观点是，与两者形成长寿命、高亲和力的键有利于实现最佳捕获。在此，我们提出了一个与之形成对比的范例，它结合了实验证据（使用IgG抗体和基质胶）、理论框架（基于多时间尺度分析）以及计算建模。与基质快速结合和解离的分子锚在纳米颗粒上的积累速度，比与基质形成高亲和力、长寿命键的分子锚快得多，从而在不使基质捕获能力饱和的情况下，显著提高了对多种入侵物种的捕获能力。我们的研究结果为设计具有精细调节亲和力的分子锚提供了蓝图，以有效增强生物凝胶对各种纳米颗粒物种的屏障特性。生物聚合物基质通常利用分子锚（如抗体）来捕获纳米颗粒。在此，作者发现，与普遍认为有效分子锚应与基质和纳米颗粒都形成强键的观点相反，弱且短寿命的锚 - 基质键具有更强的捕获能力。
