Smart lipids for programmable nanomaterials

Abstract

Novel, responsive liposomes are introduced, assembled from DNA-programmed lipids allowing sequence selective manipulation of nanoscale morphology. Short, single-stranded DNA sequences form polar head groups conjugated to hydrophobic tails. The morphology of the resulting lipid aggregates depends on sterics and electronics in the polar head groups and, therefore, is dependent on the DNA hybridization state. The programmability, specificity, and reversibility of the switchable system are demonstrated via dynamic light scattering, transmission electron microscopy, and fluorescence microscopy.

Figure 1

DNA-programmed lipid assembles to form spherical lamellar vesicles capable of switching phase to form small spherical micelles in a fully reversible fashion via DNA hybridization (+ DNA₂) and strand invasion (+ DNA₃) cycles.

Figure 2

Characterization of unilamellar vesicle structures formed from the self-assembly of DNA₁-lipid in aqueous solution. TOP: Cryogenic-TEM (cryo-TEM) images showing unilamellar bilayer morphology of the vesicles. MIDDLE: SEM of vesicles. BOTTOM: AFM data showing the flattened height profile of the vesicle structures dry, on a mica surface.

Figure 3

DNA-directed vesicle to micelle phase transition. (A) Monitored by DLS: hydrodynamic diameter (D_h). (B) Monitored by TEM (negative stain). CONDITIONS: Tris (pH 7.4, 50 mM), MgCl₂ (50 mM), DNA₁-lipid (1 μM), DNA₂ (2 μM), room temperature.

Figure 4

Specificity and reversibility of DNA-programmed phase shifting. Scale bar = 1 μm. Two different DNA-lipids were 3′-labeled with two different dyes: DNA₁-Fluorescein and DNA₄-Rhodamine. All fluorescence images are red/green channel merges. (A) Representative bright field image of labeled DNA-lipid assemblies. (B) DNA₄-Rhodamine hybridizes to DNA₅ leaving observed green fluorescence only. (C) DNA₆ (complementary to DNA₅) causes mixing of the two surfacants to give a yellow colocalized signal from both dyes. (D) DNA₁-Fluorescein hybridizes to DNA₂ to generate micelles leaving observed red fluorescence only. (E) Addition of DNA₂ and DNA₅ shifts all structures to micelles leaving little visible fluorescence. (F) Upon addition of DNA₃ (complementary to DNA₂) and DNA₆ (complementary to DNA₅), surfactants reassemble to give yellow colocalization indicative of vesicles containing both dyes. (G) DLS data of phase switching cycles with sequential ssDNA input additions. Solution conditions utilized in DLS experiment and prior to slide preparation: Tris (pH 7.4, 50 mM), MgCl₂ (50 mM), DNA-surfactant (1 μM), ssDNA input sequences (2 μM), room temperature.