Lipid-based nanoparticles
have risen to the forefront of the COVID-19 pandemic—from encapsulation of
vaccine components to modeling the virus, itself. Their rapid development in
the face of the volatile nature of the pandemic requires high-throughput,
highly flexible methods for characterization. DNA-directed patterning is a
versatile method to immobilize and segregate lipid-based nanoparticles for subsequent
analysis. DNA-directed patterning selectively conjugates oligonucleotides onto
a glass substrate and then hybridizes them to complementary oligonucleotides
tagged to the liposomes, thereby patterning them with great control and
precision. The power of this method is demonstrated by characterizing a novel
recapitulative lipid-based nanoparticle model of SARS-CoV-2 —S-liposomes— which
present the SARS-CoV-2 spike (S) protein on their surfaces. Patterning of a
mixture of S-liposomes and liposomes that display the tetraspanin CD63 into discrete
regions of a substrate is used to show that ACE2 specifically binds to
S-liposomes. Importantly, DNA-directed patterning of S-liposomes is used to
verify the performance of a commercially available neutralizing antibody
against the S protein. Ultimately, the introduction of S-liposomes to
ACE2-expressing cells demonstrates the biological relevance of DNA-directed
patterning. Overall, DNA-directed patterning enables a wide variety of custom
assays for the characterization of any lipid-based nanoparticle.
Contextualizing the biological relevance of standardized high‐resolution respirometry to assess mitochondrial function in permeabilized human skeletal muscle