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Crosslinking of Mobile Species

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.

By eliminating the need for matrix constituents to directly recognize diverse antigenic species, an anchor-matrix system can enable an effective diffusional barrier against many nanoparticulate species while maintaining relatively static biochemistry and microstructure of the matrix. This suggests that anchors, such as IgG and other Abs produced by the immune system that can adapt and bind diverse molecular entities, represent an ideal platform to control nanoparticulate transport.

Researchers from the Greg Forest Group 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. These results provide a blueprint for engineering molecular anchors with finely tuned affinities to effectively enhance the barrier properties of biogels against diverse nanoparticulate species.

June 21, 2018