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Researchers investigated how cholesterol-modified, star-shaped DNA nanomotifs anchor to the lipid bilayers of giant unilamellar vesicles and self-organize based on their sticky end sequences. DNA motifs with complementary sequences distributed uniformly across the membrane, while motifs with orthogonal, non-complementary sequences segregated into gel-like domains with restricted lateral mobility. Crucially, this DNA-driven phase separation occurred independently of lipid phase separation, demonstrating that molecular organization on the membrane surface can be controlled through DNA sequence design alone.
Why it matters
This work provides a programmable strategy for organizing molecules on synthetic membrane surfaces, which could advance the engineering of artificial cells capable of performing complex biological functions such as signaling and division. The ability to spatially control membrane components without relying on lipid composition offers greater design flexibility for building synthetic biological systems.
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Spatial organization and temporal regulation of membrane components are essential for achieving complex functions in artificial cells, such as cell division and signalling. DNA-based molecular tools provide a powerful means to control biomolecular interactions with high precision. Here, we investigate the phase behavior of cholesterol-modified, star-shaped DNA nanomotifs anchored to the lipid bilayers of giant unilamellar vesicles (GUVs), by using fluorescence confocal microscopy and cryo-electron microscopy. These motifs spontaneously anchor to the lipid bilayers via hydrophobic interactions and exhibit distinct spatial organization depending on their sticky end sequences. Motifs with complementary sticky end sequences interact and distribute uniformly, while orthogonal motifs with different sticky end sequences segregate into isolated gel-like domains with limited lateral mobility. Notably, the phase separation of motifs does not require lipid phase separation, indicating that DNA-driven organization can take place independently of lipid phase separation. The behavior of this system is governed by the interplay of three key parameters: (i) hydrophobic anchoring via cholesterol, (ii) electrostatic repulsion between negatively charged DNA nanomotifs, and (iii) sticky end interactions. The observed two-dimensional phase separation of orthogonal DNA nanomotifs at the GUV interface presents a novel strategy for controlling lateral membrane organization in GUV systems. This approach would offer flexibility in membrane composition and enables molecular positioning, thereby achieving a high degree of organization on the surface in artificial cell models.
Source: Two-Dimensional Phase Separation of DNA Nanomotifs Anchored to Lipid Bilayers