Ionophore constructed from non-covalent assembly of a G-quadruplex and liponucleoside transports K+-ion across biological membranes

Abstract

The selective transport of ions across cell membranes, controlled by membrane proteins, is critical for a living organism. DNA-based systems have emerged as promising artificial ion transporters. However, the development of stable and selective artificial ion transporters remains a formidable task. We herein delineate the construction of an artificial ionophore using a telomeric DNA G-quadruplex (h-TELO) and a lipophilic guanosine (MG). MG stabilizes h-TELO by non-covalent interactions and, along with the lipophilic side chain, promotes the insertion of h-TELO within the hydrophobic lipid membrane. Fluorescence assays, electrophysiology measurements and molecular dynamics simulations reveal that MG/h-TELO preferentially transports K +-ions in a stimuli-responsive manner. The preferential K +-ion transport is presumably due to conformational changes of the ionophore in response to different ions. Moreover, the ionophore transports K +-ions across CHO and K-562 cell membranes. This study may serve as a design principle to generate selective DNA-based artificial transporters for therapeutic applications.

G-quadruplex based biosensor: A potential tool for SARS-CoV-2 detection

“…G-rich ssDNA can fold into G-quadruplex structure under certain ionic strength ( Wu et al, 2017 ). G-quadruplex structures can specifically interact with different target molecules and are therefore used to detect metal ions ( Debnath et al, 2020 ), protein ( Margulies and Hamilton, 2009 ), biomolecules ( Wang et al, 2015b ), enzymes ( Nie et al, 2015 ) and others.…”

Development of Artificial Cell Models Using Microfluidic Technology and Synthetic Biology

“…For instance, ionomycin from Streptomyces conglobatus allows the passage of only calcium ions, valinomycin from Streptomyces fulvissimus transports potassium ions selectively, nigericin from Streptomyces hygroscopicus transports potassium and hydrogen ions, monensin from Streptomyces cinnamonensis exchanges sodium and hydrogen ions, and gramicidin from Bacillus brevis transports cations like potassium, sodium, and hydrogen ions selectively. To allow the selective exchange of ions in/out of the giant lipid vesicles, these ionophores are reconstituted in the giant lipid vesicles [116,117].…”

Cell mimicry as a bottom‐up strategy for hierarchical engineering ofnature‐inspiredentities

“…The permeability of the separating membrane itself depends on the physiochemical properties of the amphiphilic building blocks, which can be phospholipids (Bhattacharya, Brea, Niederholtmeyer, & Devaraj, 2019), polypeptides (Schreiber, Huber, & Schiller, 2019; Vogele et al, 2018), and block copolymers (Meng et al, 2005). In addition, a higher degree of control over secretion and interaction with the buffer environment was demonstrated (Debnath et al, 2020; Hilburger, Jacobs, Lewis, Peruzzi, & Kamat, 2019). Facilitation of spatially separated multi‐step enzymatic pathways in separate compartments (Elani, Law, & Ces, 2014) and incorporation of an endomembrane system (internal membrane structures within a cell‐sized carrier) to mimic the hierarchical structure of eukaryotic cells is the next step toward mimicking the architecture of a natural cell (Deng, Yelleswarapu, & Huck, 2016; Gopfrich et al, 2018; Tan et al, 2017).…”