Promoting Cell Fusion by Polyvalent DNA Ligands

Abstract

Artificially induced in vitro cell fusion is one essential technique that has been extensively used for biological studies. Nevertheless, there is a lack of robust and efficient method to produce fused cells efficiently. Herein, we proposed to use cellmembrane-anchored polyvalent DNA ligands (PDL) to bring cells into close proximity by forming clusters to enhance PEG-induced cell fusion. PDL of complementary sequences are separately anchored onto different population of cells through cholesterolinduced hydrophobic insertion into lipid membrane. Cells are clustered via mixing cells of complementary PDL prior to cell fusion. PDL exhibited strong stability on cell membrane, induced efficient cell clustering, and eventually achieved cell fusion efficiently in combination with PEG induction. We demonstrated homogeneous and heterogeneous cell fusion of high yield on various cell types. This report presented a programmable yet robust technique for achieving efficient cell fusion that hold great application potentials.

Reassembly of Peptide Nanofibrils on Live Cell Surfaces Promotes Cell–Cell Interactions

“…The values were ∼2-fold higher than that of the HeLa cells treated with only T7– f1 –PEG 2k –folate (13 ± 6.0%) or T7– f4 –PEG 2k –folate (13 ± 3.5%) [ n = 3 (SD)]. The promotions indicated the merit of the extended ligand scaffolds in facilitating multivalent ligand–receptor interactions between the cells, which has also been demonstrated in several other binding systems. − We also mixed the peptide–cell samples at 37 °C for 1 h and then decreased the temperature back to 25 °C. Enhancements in the conversion ratios of all samples were observed, which were predictable, because of faster encounter rates of entities at the higher temperature.…”

Recent Advances in DNA‐Based Cell Surface Engineering for Biological Applications

“…In contrast to ssDNA, DNA nanostructures with multiple binding sites would significantly increase the binding capability between different cell populations. [49] Inspired by polyvalent interactions observed in nature, Wang et al constructed a polyvalent DNA polymer that contains multiple recognition sites for enhancing molecular recognition and cell assembly efficiency (Figure 5A). [12] In this work, DNA initiator (DI) bearing DBCO was anchored on cell surface by copper-free click chemistry with the membrane glycoproteins and the polyvalent DNA polymers was produced by HCR.…”

“…As previously discussed, DNA molecules immobilized on cell surface could be used as recognition modules for cell assembly by DNA base‐pairing. In contrast to ssDNA, DNA nanostructures with multiple binding sites would significantly increase the binding capability between different cell populations [49] . Inspired by polyvalent interactions observed in nature, Wang et al.…”

Tuning the Extracellular Vesicles Membrane through Fusion for Biomedical Applications

“…The most studied processes involving EVs membrane fusion are endocytosis and exocytosis, whereby an EV’s membrane vesicles fuse with the cell membrane to uptake or release their contents into the intracellular or extracellular environment, respectively [ 35 , 36 , 37 , 38 ]. Numerous membrane fusion processes have been presented using a variety of molecular compositions on the plasma membrane surface that tether to or dock with membranes and bring them into close proximity; additionally, they locally disturb the membranes to reduce the energy barriers for fusion [ 39 , 40 , 41 , 42 , 43 ].…”