Bound-state diffusion due to binding to flexible polymers in a selective biofilter

Abstract

Selective biofilters are used by cells to control the transport of proteins, nucleic acids, and other macromolecules. Biological filters demonstrate both high specificity and rapid motion or high flux of proteins. In contrast, high flux comes at the expense of selectivity in many synthetic filters. Binding can lead to selective transport in systems in which the bound particle can diffuse, but the mechanisms that lead to bound diffusion remain unclear. Previous theory has proposed a molecular mechanism of bound-state mobility based only on transient binding to flexible polymers. However, this mechanism has not been directly tested in experiments. We demonstrate that bound mobility via tethered diffusion can be engineered into a synthetic gel using protein fragments derived from the nuclear pore complex. The resulting bound-state diffusion is quantitatively consistent with theory. Our results suggest that synthetic biological filters can be designed to to take advantage of tethered diffusion to give rapid, selective transport. SIGNIFICANCE Biological filters control the passage of proteins and other macromolecules between compartments of living systems. Determination of molecular mechanisms giving selective transport would enable the design of both selective filters and particles designed to penetrate biological barriers for drug delivery. One such mechanism arises from transient binding to dynamic polymer tethers. We designed a biomaterial which supports this type of tethered diffusion, demonstrating the potential to engineer bio-inspired filters.

Enhanced diffusion by reversible binding to active polymers

“…In the first example, the ratio τ R /τ b is fixed at a value of 0.8 which is so chosen to represent the relevant range of length scales l c = 1 − 2 L p in biological systems like the nuclear pore complex. 35,36 ity. The plots in Fig.…”