#14 - Modular and Programable Partitioning of Biomimetic DNA Nanostructures in Lipid Domains

Roger Rubio Sanchez (University of Cambridge)

Monday, 30 Nov 21:15 - 22:00 CET

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Abstract

Title: Modular and Programable Partitioning of Biomimetic DNA Nanostructures in Lipid Domains

Author(s): Roger Rubio-Sanchez^a, Simone Eizagirre-Barker^a, Michal Walczak^a, Pietro Cicuta^a, Lorenzo Di Michele^a,b

Affiliations: ^aUniversity of Cambridge, ^bImperial College London

Abstract: Biological membranes, dauntingly complex interfaces, feature diverse proteo-lipid systems that facilitate a breadth of biochemical processes, such as sensing and transduction of signals [1]. Cells overcome their heterogeneity by forming lipid rafts, clusters of lipids where proteins selectively and dynamically co-localise via lipophilic modifications that bestow them with raft affinity [2]. Bottom-up synthetic biology aims at emulating biological functionalities in minimal systems, with applicability ranging from biosynthesis to smart therapeutics [3]. These artificial cells, often prepared from synthetic multi-component lipid membranes, can display phase separation [4]. In turn, DNA nanotechnology, an increasingly adopted route for biomimicry, readily enables interfacing DNA architectures with bio-inspired lipid bilayers by tagging them with a hydrophobic moiety, where they also partition [5] in a way that reminisces of the lateral affinity proteins have for raft microenvironments [6]. Here, we engineer DNA nanostructures to program their partitioning in phase-separated model membranes. By exploiting the affinity cholesterol and tocopherol motifs have respectively for liquid-ordered (Lo) and liquid-disordered (Ld) domains, we modulate their lateral distribution by combining multiple anchors, changing nanostructure size, and topology. We exemplify the functionality of our approach with a biomimetic DNA nano-architecture, which dynamically undergoes ligand-induced reconfiguration to achieve cargo transport through lateral re-distribution between phases. Our findings [7] showcase the synergy between the partitioning of DNA-based nanostructures and lipid phase separation, paving the way for the development of next-generation bio-inspired platforms for sensing and communication in artificial cells.

References

[1] Noireaux, Vincent, Yusuke T. Maeda, and Albert Libchaber. “Development of an Artificial Cell, from Self-Organization to Computation and Self-Reproduction.” Proceedings of the National Academy of Sciences 108, no. 9 (March 1, 2011): 3473–80. https://doi.org/10.1073/pnas.1017075108.

[2] Simons, Kai, and Derek Toomre. “Lipid Rafts and Signal Transduction.” Nature Reviews Molecular Cell Biology 1, no. 1 (October 2000): 31–39. https://doi.org/10.1038/35036052.

[3] Oglęcka, Kamila, Padmini Rangamani, Bo Liedberg, Rachel S Kraut, and Atul N Parikh. “Oscillatory Phase Separation in Giant Lipid Vesicles Induced by Transmembrane Osmotic Differentials.” Edited by Randy Schekman. ELife 3 (October 15, 2014): e03695. https://doi.org/10.7554/eLife.03695.

[4] Veatch, Sarah L., and Sarah L. Keller. “Miscibility Phase Diagrams of Giant Vesicles Containing Sphingomyelin.” Physical Review Letters 94, no. 14 (April 13, 2005): 148101. https://doi.org/10.1103/PhysRevLett.94.148101.

[5] Beales, Paul A., and T. Kyle Vanderlick. “Application of Nucleic Acid–Lipid Conjugates for the Programmable Organisation of Liposomal Modules.” Advances in Colloid and Interface Science, Special Issue: Helmuth Möhwald Honorary Issue, 207 (May 1, 2014): 290–305. https://doi.org/10.1016/j.cis.2013.12.009.

[6] Lorent, Joseph H., Blanca Diaz-Rohrer, Xubo Lin, Kevin Spring, Alemayehu A. Gorfe, Kandice R. Levental, and Ilya Levental. “Structural Determinants and Functional Consequences of Protein Affinity for Membrane Rafts.” Nature Communications 8, no. 1 (October 31, 2017): 1219. https://doi.org/10.1038/s41467-017-01328-3.

[7] Rubio-Sánchez, R., Eizagirre-Barker, S., et.al In preparation.