Water Dynamics in a Peptide-appended Pillar[5]arene Artificial Channel in Lipid and Biomimetic Membranes

Peptide-appended Pillar[5]arene (PAP) is an artificial water channel that can be incorporated into lipid and polymeric membranes to achieve high permeability and enhanced selectivity for angstrom-scale separations [Shen et al. Nat. Commun.9:2294 (2018)]. In comparison to commonly studied rigid carbon nanotubes, PAP channels are conformationally flexible, yet these channels allow a high water permeability [Y. Liu and H. Vashisth Phys. Chem. Chem. Phys.21:22711 (2019)]. Using molecular dynamics (MD) simulations, we study water dynamics in PAP channels embedded in biological (lipid) and biomimetic (block-copolymer) membranes to probe the effect of the membrane environment on water transport characteristics of PAP channels. We have resolved the free energy surface and local minima for water diffusion within the channel in each type of membrane. We find that water follows single file transport with low free-energy barriers in regions surroundings the central ring of the PAP channel and the single file diffusivity of water correlates with the number of hydrogen bonding sites within the channel, as is known for other sub-nm pore-size synthetic and biological water channels [Horner et al. Sci. Adv.1:e1400083 (2015)].

Unidirectional Single-File Transport of Full-Length Proteins Through a Nanopore

Nanopore technology offers long, accurate sequencing of an DNA or RNA strand via enzymatic ratcheting of the strand through a nanopore in single nucleotide steps, producing stepwise modulations of the nanopore ion current. In contrast to nucleic acids, their daughter molecules, proteins, have neutral peptide backbones and side chains of varying charges. Further, proteins have stable secondary and higher order structures that obstruct protein linearization required for single file nanopore transport. Here, we describe a general approach for realizing unidirectional transport of proteins through a nanopore that neither requires the protein to be uniformly charged nor a pull from a biological enzyme. At high concentrations of guanidinium chloride, we find fulllength proteins to translocate unidirectionally through an a-hemolysin nanopore in a polymer-based membrane, provided that one of the protein ends is decorated with a short anionic peptide. Molecular dynamics simulations show that such surprisingly steady protein transport is driven by a giant electro-osmotic effect caused by binding of guanidinium cations to the inner surface of the nanopore. We show that ionic current signals produced by protein passage can be used to distinguish two biological proteins and the global orientation of the same protein (N-to-C vs. C-to-N terminus) during the nanopore transport. With the average transport rate of one amino acid per 10 μs, our method may enable direct enzyme-free protein fingerprinting or perhaps even sequencing when combined with a high-speed nanopore reader instrument.

Modeling and optimization of hourglass-shaped aquaporins

This paper is concerned with aquaporins (AQPs), that are proteins playing the role of water-selective channels also called nanopores, involved in many biological systems. From a technological point of view, it is relevant to design systems enjoying as good filtration properties. Inspired by [S. Gravelle, L. Joly, C. Ybert and L. Bocquet, Large permeabilities of hourglass nanopores: From hydrodynamics to single file transport, J. Chem. Phys. 141 (2014) 18C526], we investigate in a quite general framework shape optimization issues related to the improvement of hourglass-shaped aquaporins performances, in terms of energy dissipated by the fluid through the channel. After modeling this problem mathematically, we show that it is well-posed in some sense, and compute the so-called shape derivative of the cost functional in view of numerical simulations. Noting that our framework requires regularity properties of the free boundary, we introduce a dedicated numerical method, using in particular a proper shape gradient extension-regularization to adapt the mesh at each iteration, in an adequate way. Optimal shapes of aquaporins are then provided for relevant values of parameters, and we finally discuss the observed performances with respect to the existing results/literature.

Single-file transport of water through membrane channels

After a short introduction into the single-file transport theory, we analyze experiments in which the unitary water permeability, pf, of water channel proteins (aquaporins, AQPs), potassium channels (KcsA), and antibiotics (gramicidin-A derivatives) has been obtained. A short outline of the underlying methods is also provided.

Ultra-fast single-file transport of a simple liquid beyond the collective behavior zone

Breakdown of the collective single-file behavior leads to ultra-fast transport of a simple liquid.