An Abiotic Analogue of the Nuclear Pore Complex Hydrogel

Bird, Sean P.; Baker, Lane A.

doi:10.1021/bm200820x

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…However, various highly selective membrane transport processes found in living systems are based on attractive yet transient interactions between macromolecular cargo and biological membrane barriers . For example, importins pass through the nuclear envelope via transient, low-affinity hydrophobic interactions with the phenylalanine-glycine domains of nuclear pore complexes (NPCs). , The unveiling of this unique transport mechanism has stimulated recent efforts in incorporating NPC-derived protein sequences to develop biomaterials that replicate NPC functions. − In contrast to these biological transport systems, which have been optimized through evolution, synthetic transport systems rarely exploit transient interactions to achieve selectivity, due to the difficulties associated with fine-tuning cargo–barrier interactions. , …”

Section: Introductionmentioning

confidence: 99%

A General DNA-Gated Hydrogel Strategy for Selective Transport of Chemical and Biological Cargos

Distler

Cheng

et al. 2021

J. Am. Chem. Soc.

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The selective transport of molecular cargo is critical in many biological and chemical/materials processes and applications. Although nature has evolved highly efficient in vivo biological transport systems, synthetic transport systems are often limited by the challenges associated with fine-tuning interactions between cargo and synthetic or natural transport barriers. Herein, deliberately designed DNA−DNA interactions are explored as a new modality for selective DNA-modified cargo transport through DNA-grafted hydrogel supports. The chemical and physical characteristics of the cargo and hydrogel barrier, including the number of nucleic acid strands on the cargo (i.e., the cargo valency) and DNA−DNA binding strength, can be used to regulate the efficiency of cargo transport. Regimes exist where a cargo−barrier interaction is attractive enough to yield high selectivity yet high mobility, while there are others where the attractive interactions are too strong to allow mobility. These observations led to the design of a DNA-dendron transport tag, which can be used to universally modify macromolecular cargo so that the barrier can differentiate specific species to be transported. These novel transport systems that leverage DNA−DNA interactions provide new chemical insights into the factors that control selective cargo mobility in hydrogels and open the door to designing a wide variety of drug/probe-delivery systems.

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Section: Introductionmentioning

confidence: 99%

A General DNA-Gated Hydrogel Strategy for Selective Transport of Chemical and Biological Cargos

Distler

Cheng

et al. 2021

J. Am. Chem. Soc.

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“…The self diffusivity of proteins in crowded solutions has been shown to be slowed down to one fifth of the dilute limiting value [11]. Also diffusion of proteins across the nuclear pore complex (NPC) [12][13][14][15][16][17][18] is an example of diffusion in a crowded environment where the crowding is due to the presence of proteins called nucleoporins that are rich in hydrophobic amino acids and form a brush [19,20] or a reversible hydrogel [20,21]. Proteins diffusing through NPC bind to these nucleoporins and experience a slowdown.…”

Section: Introductionmentioning

confidence: 99%

Tracer diffusion in a crowded cylindrical channel

et al. 2013

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Based on a coarse-grained model, we carry out molecular dynamics simulations to analyze the diffusion of a small tracer particle inside a cylindrical channel whose inner wall is covered with randomly grafted short polymeric chains. We observe an interesting transient subdiffusive behavior along the cylindrical axis at high attraction between the tracer and the chains, however, the long-time diffusion is always normal. This process is found to be enhanced for the case that we immobilize the grafted chains, i.e., the subdiffusive behavior sets in at an earlier time and spans over a longer time period before becoming diffusive. Even if the grafted chains are replaced with a frozen sea of repulsive, nonconnected particles in the background, a transient subdiffusion is observed. The intermediate subdiffusive behavior only disappears when the grafted chains are replaced with a mobile background sea of mutually repulsive particles. Overall, the long-time diffusion coefficient of the tracer along the cylinder axis decreases with an increase in system volume fraction, the strength of the attraction between the tracer and the background, and also on freezing the background.

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“…Specifically, a solid-state nanopore was modified with FG-rich nups to detect the translocation of single protein molecules through the single pore as real-time conductance blockage . Biomimetic NPCs were impermeable to large proteins (>40 kDa), which were transported only as complexes with transport receptors, i.e., importins, as also demonstrated by authentic NPCs, , as well as hydrogels of isolated FG nups. , Moreover, the conductance of solid-state nanopore was largely reduced by modification with isolated FG nups and was quantitatively analyzed to conclude that ion transport is completely blocked when the density of FG units exceeded 85 mg/mL . The lowered conductance of single NPC mimetic was consistent with that of single authentic NPCs, which was much lower than expected for nonblocking pores with ∼40 nm diameters .…”

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confidence: 99%

Probing High Permeability of Nuclear Pore Complexes by Scanning Electrochemical Microscopy: Ca²⁺ Effects on Transport Barriers

et al. 2019

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The nuclear pore complex (NPC) solely mediates molecular transport between the nucleus and cytoplasm of a eukaryotic cell to play important biological and biomedical roles. It, however, is not well understood chemically how this biological nanopore selectively and efficiently transports various substances including small molecules, proteins, and RNAs by using transport barriers that are rich in highly disordered repeats of hydrophobic phenylalanine and glycine intermingled with charged amino acids. Herein, we employ scanning electrochemical microscopy to image and measure the high permeability of NPCs to small redox molecules. The effective medium theory demonstrates that the measured permeability is controlled by diffusional translocation of probe molecules through water-filled nanopores without steric or electrostatic hindrance from hydrophobic or charged regions of transport barriers, respectively. The permeability of NPCs, however, is lowered by a low millimolar concentration of Ca 2+ , which can interact with anionic regions of transport barriers to alter their spatial distributions within the nanopore. We employ atomic force microscopy to confirm that transport barriers of NPCs are dominantly recessed (~80%) or entangled (~20%) at the high Ca 2+ level in contrast to authentic populations of entangled (~50%), recessed (~25%), and "plugged" (~25%) conformations at a physiological Ca 2+ level of sub-micromolar. We propose a model for synchronized Ca 2+ effects on the conformation and permeability of NPCs, where transport barriers are viscosified to lower permeability. Significantly, this result supports a hypothesis that the functional structure of transport barriers is maintained not only by their hydrophobic regions, but also by charged regions.

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An Abiotic Analogue of the Nuclear Pore Complex Hydrogel

Cited by 7 publications

References 25 publications

A General DNA-Gated Hydrogel Strategy for Selective Transport of Chemical and Biological Cargos

A General DNA-Gated Hydrogel Strategy for Selective Transport of Chemical and Biological Cargos

Tracer diffusion in a crowded cylindrical channel

Probing High Permeability of Nuclear Pore Complexes by Scanning Electrochemical Microscopy: Ca²⁺ Effects on Transport Barriers

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An Abiotic Analogue of the Nuclear Pore Complex Hydrogel

Cited by 7 publications

References 25 publications

A General DNA-Gated Hydrogel Strategy for Selective Transport of Chemical and Biological Cargos

A General DNA-Gated Hydrogel Strategy for Selective Transport of Chemical and Biological Cargos

Tracer diffusion in a crowded cylindrical channel

Probing High Permeability of Nuclear Pore Complexes by Scanning Electrochemical Microscopy: Ca2+ Effects on Transport Barriers

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Probing High Permeability of Nuclear Pore Complexes by Scanning Electrochemical Microscopy: Ca²⁺ Effects on Transport Barriers