An Artificial Molecular Shuttle Operates in Lipid Bilayers for Ion Transport

Abstract

Inspired by natural biomolecular machines, synthetic molecular-level machines have been proven to perform well-defined mechanical tasks and measurable work. To mimic the function of channel proteins, we herein report the development of a synthetic molecular shuttle, [2]­rotaxane 3, as a unimolecular vehicle that can be inserted into lipid bilayers to perform passive ion transport through its stochastic shuttling motion. The [2]­rotaxane molecular shuttle is composed of an amphiphilic molecular thread with three binding stations, which is interlocked in a macrocycle wheel component that tethers a K+ carrier. The structural characteristics enable the rotaxane to transport ions across the lipid bilayers, similar to a cable car, transporting K+ with an EC50 value of 1.0 μM (3.0 mol % relative to lipid). We expect that this simple molecular machine will provide new opportunities for developing more effective and selective ion transporters.

A Molecular Cable Car for Transmembrane Ion Transport

“…Nevertheless, an example of a synthetic molecular machine that can carry ions across a membrane by exploiting its intercomponent motion was still missing. Very recently, a group at East China University of Science and Technology in Shanghai designed, synthesized, and investigated an artificial molecular machine that can operate in a bilayer membrane and passively carry K + ions across it …”

“…Very recently,agroup at East China University of Science and Te chnology in Shanghai designed, synthesized, and investigated an artificial molecular machine that can operate in ab ilayer membrane and passively carry K + ions across it. [8] Thet ransporter is am olecular shuttle,t hat is,ar otaxane in which the mechanically interlocked ring and axle components can slide relatively to one another. [5] As pecies of this kind is indeed an interesting candidate to realize ap assive transmembrane transporter,because 1) its chemical structure and one-dimensional nature could favor ap erpendicular insertion in the bilayer, 2) its length can be designed such that the thermally driven stochastic linear movement of the ring along the axle covers the membrane thickness,and 3) its ring component can be equipped with adocking site for the cargo to be transported.…”

Artificial Signal Transduction across Membranes

“…[196,197] The systems mentioned in this section were classified as carriers due to an explicit conformationalc hange, or movement through the membrane to pick up cargo,t hereby demonstrating ad ifferent mode of action than the artificial ion channels. [205] The shuttlei sc omposed of an amphiphilic molecular thread with three bindings tations,through which am acrocycle tethered to aK + carrierc ould translocate from one side of the bilayer to the other.T his last example illustrates the interest in developing bio-inspired molecular machines. [202] Transport was proposed to occur through an uncomplexed carrier diffusing into the vesicle,w here it coordinated with the salt, and subsequent diffusing of the carrier-saltc omplex out of the vesicle.…”

“…[223] Figure 6. [205] C) Polymerisation of DNA origamic urls into long helical structures induces and stabilises lipid tubules in GUVs. A) Proposed mechanism of am olecular umbrella design that selectively transports ATPo ver glutathione across alipid bilayer.T op left to bottom right:bindingofhydrophilic cargo to the umbrella is followed by aconformational change in the scaffold to shield the cargo upon bilayer insertion,and finallyre-opening of the umbrella to release the cargo on the other sideo ft he membrane.…”

“…[203,204] More recently,i nspired by biomolecular machinery,ar otaxanem olecular shuttle was developed that could transport K + across lipid membranes ( Figure 6B). [205] The shuttlei sc omposed of an amphiphilic molecular thread with three bindings tations,through which am acrocycle tethered to aK + carrierc ould translocate from one side of the bilayer to the other.T his last example illustrates the interest in developing bio-inspired molecular machines. [206,207] True artificial transmembrane machines should be capable of actively transporting substrates against their electrochemical gradient by consuming another type of energy.T ot his extent, two notable examples should be mentioned that realised the build-up of at ransmembrane proton gradient by using light as an energys ource.…”