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 take advantage of tethered diffusion to give rapid, selective transport.

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 Fig. 4 depicts the plot of effective diffusivity in terms of N and p for three different chain temperatures with (a) T a = T , (b) T a = 5 T , and (c) T a = 20 T .…”

“…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 such as the NPC. , Figure depicts the plot of effective diffusivity in terms of N and p for three different chain temperatures with (a) T a = T , (b) T a = 5 T , and (c) T a = 20 T . In the passive case with T a = T , the maximum diffusivity is the free diffusivity of the plate D f and occurs when there are no bound chains.…”

Physics of the nuclear pore complex: Theory, modeling and experiment

“…Using a simplified model of FG nup flexibility and transport protein transfer between FG nups, an analytical expression was obtained for the diffusion coefficient in the bound state in the case of a transport protein with two binding sites (NTF2) [265,269]. Similar ideas were used in [267,270] for particles with multiple binding sites.…”

“…These models can be extended to explicitly include the binding-unbinding kinetics of the proteins by considering the protein diffusion in the bound and the unbound states [49,265,267,269,277]. These models of in-channel diffusion, illustrated in Fig.…”

“…Although the exact dependence of D in on the interaction strength is still unknown, a number of models predict that it is decreased by the binding to the polymers (see Section 4.1.1). In this case, this effect can balance the increase in the translocation probability due to binding, resulting in the maximization of transport at an optimal interaction strength [265,269]. This may provide the foundation for the transport selectivity of the NPC, whereby translocation though the NPC is only favored for transport protein-cargo complexes with an effective affinity in a certain range (Fig.…”