Department of Chemical Engineering , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
Biomacromolecules. 2018 Oct 8;19(10):3905-3916. doi: 10.1021/acs.biomac.8b00556. Epub 2018 Sep 5.
Biological systems routinely regulate biomolecular transport with remarkable specificity, low energy input, and simple mechanisms. Here, the biophysical mechanisms of nuclear transport inspire the development of gels for recognition and selective permeation (GRASP). GRASP presents a new paradigm for specific transport and selective permeability, in which binding interactions between a biomolecule and a hydrogel lead to faster penetration of the gel. A molecular transport theory identifies key principles for selective transport: entropic repulsion of noninteracting molecules and affinity-mediated diffusion of multireceptor biomolecules through a walking mechanism. The ability of interacting molecules to walk through hydrogels enables enhanced permeability in polymer networks. To realize this theoretical prediction in a novel material, GRASP is engineered from a poly(ethylene glycol) network (entropic barrier) containing antibody-binding oligopeptides (affinity domains). GRASP is synthesized using simultaneous bioconjugation and polycondensation reactions. The elastic modulus, characteristic pore size, biomolecular diffusivity, and selective permeability are measured in the resulting materials, which are applied to regulate the transport of equally sized molecules by preferentially transporting a monoclonal antibody from a polyclonal mixture. Overall, this work presents rationally designed, nucleopore-inspired hydrogels that are capable of controlling biomolecular transport.
生物系统通常以显著的特异性、低能量输入和简单的机制来调节生物分子的运输。在这里，核运输的生物物理机制激发了用于识别和选择性渗透（GRASP）的凝胶的发展。GRASP 为特定运输和选择性渗透性提供了一个新的范例，其中生物分子与水凝胶之间的结合相互作用导致凝胶更快地渗透。分子运输理论确定了选择性运输的关键原则：非相互作用分子的熵斥力以及通过行走机制扩散多受体生物分子的亲和力介导。相互作用分子在水凝胶中行走的能力使聚合物网络中的渗透性增强。为了在新型材料中实现这一理论预测，GRASP 是由含有抗体结合寡肽（亲和结构域）的聚乙二醇网络（熵屏障）设计而成的。GRASP 是使用同时的生物共轭和缩聚反应合成的。在所得材料中测量弹性模量、特征孔径、生物分子扩散率和选择性渗透性，并将其应用于通过优先从多克隆混合物中运输单克隆抗体来调节等大小分子的运输。总的来说，这项工作提出了经过合理设计、受核孔启发的水凝胶，能够控制生物分子的运输。
