Lipid-DNA Conjugates for Cell Membrane Modification, Analysis, and Regulation

A lipid, an important component of living cells, is chemically defined as a substance that is insoluble in water and soluble in alcohol, ether, and chloroform. While DNA is the chemical name for the molecule that carries genetic instructions in all living things. By chemically linking these two natural compounds together, synthetic lipid-DNA conjugates exhibit several attractive features for cell membrane studies.

This review, written by a research team from the Department of Chemistry, University of Massachusetts, demonstrates the design, structure of lipid-DNA conjugates, as well as exciting applications from generating cell membrane nanopores to transmembrane cargo deliveries, and from analyzing cell membrane events to tissue engineering.

• Lipid-DNA Conjugates

Lipids and DNAs are two major classes of biological macro-molecules, and various biological structures have been constructed based on either just lipid or DNA. Recent studies have found that by chemically conjugating hydrophobic molecules and DNAs together, several attractive features for cellular applications can be developed.

These lipid-DNA conjugates show some features. Firstly, the highly controllable and programmable DNA self-assemblies can be used to fine-tune the conjugation pattern and structure of lipids. Then, DNA can be easily modified with various functional moieties. Meanwhile, the lipid modification can recruit DNAs to either penetrate through the cell membranes or simply immobilize onto the plasma membrane surfaces.

• Applications of Lipid-DNA Conjugates

Lipid-DNA conjugates for generating artificial membrane nanopores

Nanopores are structures containing hollow cores of nanometer sizes. In cell membranes, nanopores are normally formed by a cluster of proteins for molecular transportations.

A new class of membrane-anchored DNA nanopores has been recently introduced, which has been applied to facilitate transmembrane molecular flux, drug delivery, or biosensing. They can also be further modified to be an interesting approach for targeted disease therapeutics by precisely regulating the open and close state of these artificial membrane channels. Lipid-modified DNA nanopores are potential to be the next-generation platform for developing bio-sensors, tuning membrane permeabilities, and transporting specific cargos.

Lipid-DNA conjugates for tissue engineering

Lipid-DNA conjugates have been proved to precisely arrange how different cells can contact with each other. For example, a research team has already successfully built custom tissues as big as several centimeters.

So far, the realization of applying these lipid-DNA conjugates to build up tissues or organs has not been demonstrated yet. But these conjugates have shown great potential in precisely regulating the assemblies of single cell type or several different types of cells.

Lipid-DNA conjugates for cell membrane analysis

By conjugating DNA strands with natural plasma membrane lipids, these lipid-DNA conjugates could dramatically advance our understanding of the structures and functions of cell membranes in health and disease. Indeed, these lipid-DNA probes can be potentially used to study many previously inaccessible cell membrane events.

For example, a research team has developed a lipid-DNAzyme-based fluorescent sensor for realtime monitoring of metal ion level in the extracellular microenvironments. Other related research results include the lipid-modified DNA G-quadruplex sensor for ratiometric probing of signaling molecules in the cell membranes, using lipid-DNA conjugates to monitor transient lipid-lipid interactions on live cell membranes, etc.

Lipid-DNA conjugates for studying mechanobiology

Lipid-DNA conjugates can also be used to study biophysical signal transduction at cell-cell junctions, including tissue expansion, stretching, migration, proliferation, and differentiation.

Based on lipid-DNA conjugates, the research group writing this article has developed a membrane DNA tension probe for monitoring tensile forces at cell-cell junctions, and these probes have been used to study two mechanosensitive transmembrane proteins, integrin and E-cadherin, which have been proved to be potentially useful to study heterogeneous force patterns in a collective cell system.

Lipid-DNA conjugates for cargo deliveries

Another useful application of lipid-DNA conjugates is for transmembrane delivery of cargos. Lipid-DNA nanostructures have shown great potential as a platform for both drug delivery and bioimaging. These biocompatible nanoassemblies are structurally tunable and biological stable, and the size and shape of these lipid-DNA conjugates can be predictably controlled.

For example, scientists have developed lipid-DNA conjugates as spherical micelles with narrow size distributions and stable structures for in vivo cell membrane modification and local enrichment of therapeutic DNAs at the tumor site.

• Cell-Nucleic Acids Conjugate (CNAC) Service
• Cell-Fucose Conjugate (CFC) Service
• Cell-Peptide Conjugate (CPC) Service
• Cell-Fluorescent Protein Conjugate (CFPC) Service
• Cell-Drug Conjugate (CDC) Service
• Cell-Adjuvant-loaded Nanoparticles (CALNP) Service
• Cell-Antibody Conjugate（CAC）Service