Nucleoporin-inspired hydrogel design for selective purification of biomolecules

초록

The natural filtering systems (extracellular matrix, the nuclear pore, mucus, and bacterial biofilms, selectively and effectively separate biomolecules. In nuclear pore, rapid passage of macromolecules with high selectivity (< 0.1% of all proteins are allowed) was observed with the help of mesh-like hydrogel called nucleoporin. The dense nucleoporin network rejects large molecules (> 5 nm, 40 kDa) by its network pore size. However, some molecules overcome this entropic barrier if there is a binding affinity between nucleoporin and transporting molecules. Although the mechanisms by which the natural system handles selective filtering have not been clarified yet, this finding suggests bio-inspired approaches to the design of selective sequestration and barrier materials based on peptide-functionalized synthetic polymers. The hydrogels for recognition and selective permeation (GRASP) was engineered based on two main factors involve in selective separation (entropic repulsion and binding affinity). To promote selective permeation of target molecules dominantly, the peptides in GRASP are designed with diverse dissociation constants (Kd) for the various strength of binding affinity. The GRASP successfully rejected non-specific polyclonal antibodies, whereas specifically allowed monoclonal antibodies. The rationally designed nucleoporin-inspired hydrogels showed high potential of tuning permeability and selectivity of biomolecules for separation technologies.