Biomimetic Nanotubes Based on Cyclodextrins for Ion-Channel Applications

Abstract

Biomimetic membrane channels offer a great potential for fundamental studies and applications. Here, we report the fabrication and characterization of short cyclodextrin nanotubes, their insertion into membranes, and cytotoxicity assay. Mass spectrometry and high-resolution transmission electron microscopy were used to confirm the synthesis pathway leading to the formation of short nanotubes and to describe their structural parameters in terms of length, diameter, and number of cyclodextrins. Our results show the control of the number of cyclodextrins threaded on the polyrotaxane leading to nanotube synthesis. Structural parameters obtained by electron microscopy are consistent with the distribution of the number of cyclodextrins evaluated by mass spectrometry from the initial polymer distribution. An electrophysiological study at single molecule level demonstrates the ion channel formation into lipid bilayers, and the energy penalty for the entry of ions into the confined nanotube. In the presence of nanotubes, the cell physiology is not altered.

Versatile cyclodextrin nanotube synthesis with functional anchors for efficient ion channel formation: design, characterization and ion conductance

“…β-CD and PPO with a molecular mass of 2000 g mol −1 (β-CDNT2000), γ-CD and PIB with a molecular mass of 2300 and 20 000 g mol −1 (γ-CDNT2300 and γ-CDNT20000, respectively) and γ-CD with two chains of PEO for a molecular mass of 1000 g mol −1 (γ-CDNT1000″). The synthesis of α-CDNTs has been previously described; 79 the preparation scheme is recalled in ESI Scheme S1. † MALDI-TOF MS analysis is performed both in linear and reflector modes to probe the various mass distributions and to attribute each peak in relation to the diversity of the structural content.…”

“…89,90 Recently, we successfully manufactured and characterized short biomimetic NTs based on α-CD with a sub-nanometric diameter. 79 We showed that these NTs form spontaneous transient ion channels in lipid membranes, the conductance of which was mainly due to the transport of ions. Interestingly, under our previous experimental conditions, these NTs did not alter the mitochondrial dehydrogenase activity or the morphology of living cells.…”

“…77,78 To overcome this hurdle, we previously decided to use natural and biocompatible molecules, such as cyclodextrins (CDs), to manufacture short nanotubes to form biomimetic ion channels. 79 Modified CDs are well-known to form transition-conducting channels [80][81][82][83][84] and have also been used as molecular adaptors to improve the sensitivity of the nanopore itself. 85 CDs are natural cyclic oligosaccharides obtained by enzymatic conversion of starch.…”

Smart polymer-based calcium-ion self-regulated nanochannels by mimicking the biological Ca2+-induced Ca2+ release process

“…Within this context, much attention has been devoted to smart polymer-based 22 nanochannels, which bear the obvious advantages of high controllability, satisfactory reversibility, and remarkable conformational transition in response to external stimuli 23,24 . By producing diverse external stimuli, such as temperature, pH, light, or redox potential [25][26][27] , reversible tuning of ion transport across smart polymer-modified nanochannels can be achieved, which has resulted in wide applications for both material sciences and life sciences [28][29][30][31][32] .…”

Solid-State Nanopore Easy Chip Integration in a Cheap and Reusable Microfluidic Device for Ion Transport and Polymer Conformation Sensing

“…In contrast, nanopores have similar nanometric length and diameter. They consist of either synthesized [17][18][19][20] or proteic 21,22 channels inserted in a lipid bilayer, or of a solid-state nanopore pierced in an ultra-thin dielectric membrane. 8,12,[23][24][25][26][27][28][29][30] The main advantage of protein channels is the reproducibility of their structure and their sensitiv-ity.…”