DNA Hybridization‐Mediated Liposome Fusion at the Aqueous Liquid Crystal Interface

Abstract

The prominence of receptor-mediated bilayer fusion in cellular biology motivates development of biomimetic strategies for studying fusogenic mechanisms. An approach is reported here for monitoring receptor-mediated fusion that exploits the unique physical and optical properties of liquid crystals (LC). PEG-functionalized lipids are used to create an interfacial environment capable of inhibiting spontaneous liposome fusion with an aqueous/LC interface. Then, DNA hybridization between oligonucleotides within bulk phase liposomes and a PEG-lipid monolayer at an aqueous/LC interface is exploited to induce receptor-mediated liposome fusion. These hybridization events induce strain within the liposome bilayer, promote lipid mixing with the LC interface, and consequently create an interfacial environment favoring re-orientation of the LC to a homeotropic (perpendicular) state. Furthermore, the bi-functionality of aptamers is exploited to modulate DNA hybridization-mediated liposome fusion by regulating the availability of the appropriate ligand (i.e., thrombin). Here, a LC-based approach for monitoring receptor (i.e., DNA hybridization)-mediated liposome fusion is demonstrated, liposome properties that dictate fusion dynamics are explored, and an example of how this approach may be used in a biosensing scheme is provided.

Design of Responsive and Active (Soft) Materials Using Liquid Crystals

“…These surfaces induced an ordering transition in the LC when the ssDNA complements of the strands at the interface were introduced into the bulk aqueous solution (49). Further work by the same group showed that these ssDNA-modified interfaces could be used to capture and report liposomes decorated with complementary ssDNA strands (Figure 5 e ) (54). Overall, these examples serve to illustrate the diversity of designs of LC materials based on LC-aqueous interfaces that respond to specific biochemical transformations.…”

“…In addition to these unresolved questions, and building from the results presented in this review, the authors of this paper judge that the following areas of research are particularly fertile ones for future investigation: DNA-coupled LCs. Several studies mentioned in this review address the interactions of DNA and LCs (35, 48, 49, 54). Because DNA can be assembled into a range of nanostructures based on sequence-specific interactions, and because the ordering of LCs is particularly sensitive to the presence of structure on these length scales, the use of DNA-programmed systems to trigger and regulate ordering in LC systems appears to be a particularly promising area of future research for the design of responsive materials.LC-templated synthesis of patchy particles.…”

Controlled Peptide-Mediated Vesicle Fusion Assessed by Simultaneous Dual-Colour Time-Lapsed Fluorescence Microscopy

“…Numerous model systems for membrane fusion have been developed in recent years, all of which have employed a diverse range of molecules as fusogens. Examples of such fusogens include: hydrogen bonding motifs 1 , DNA [2][3][4][5][6][7][8][9][10][11] , PNA [12][13][14] , coiled-coil peptides [15][16][17][18] , and small molecule recognition motifs [19][20][21][22][23] . These systems exhibit varying efficiencies of fusion: some only facilitate hemifusion, or lipid-mixing; whereas others promote full fusion, resulting in content-mixing.…”

Design and application of stimulus-responsive droplets and bubbles stabilized by phospholipid monolayers

“…Upon adsorption of certain types of surfactants, the orientation of a LC can transition to homeotropic; i.e., the LC director is aligned perpendicular to the interface [14 -16]. Such observations pertaining to the change of LC orientation based on interfacial composition at the surface have led to applications in protein detection via macromolecular adsorption [17] or DNA hybridization [18,19].…”