#30 - Responsive DNA particles destabilise lipid bilayers

Michal Walczak (University of Cambridge)

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

Access to the BigBlueButton rooom for this Mini Talk via the lists for Monday and Tuesday.

Please make yourself familiar with BigBlueButton before you join the Mini Talk - read the instructions.

Abstract

Title: Responsive DNA particles destabilise lipid bilayers

Author(s): Michal Walczak^a, Ryan A. Brady^b, Leonardo Mancini^a, Roger Rubio-Sanchez^a, Claudia Contini^c, William T. Kaufhold^a,c, Pietro Cicuta^a, Lorenzo Di Michele^c,a

Affiliation(s): ^aBiological and Soft Systems, Cavendish Laboratory, University of Cambridge, Cambridge, United Kingdom; ^bDepartment of Chemistry, Faculty of Natural and Mathematical Sciences, King’s College London, London, United Kingdom; ^cMolecular Sciences Research Hub, Department of Chemistry, Imperial College London, London, United Kingdom

Abstract: Lipid bilayers play an important role in cellular biology as they act as the filter between the inside and outside of the cell. Their integrity, often associated with a proper functioning and vitality of the cells, can be compromised by a number of biological and synthetic agents, including antimicrobial peptides, amyloid aggregates, polymer particles and metal particles with charged coating. Such agents, frequently considered to be toxic and highly undesirable, have a variety of beneficial applications as the ability to control membrane leakage can be harnessed for the purpose of biosensing and therapeutic agent delivery. Here, we present a novel type of synthetic, DNA-based particles capable of disrupting lipid membranes [1]. The particles have a core-shell structure and self-assemble from cholesterol-DNA nanostructures, named C-stars [2,3,4], responsible for the formation of membrane-adhesive core, and all-DNA nanoconstructs forming a protective hydrophilic corona around the core. These aggregates are stable in solution in the presence of liposomes and their size can be fully controlled through a change of the incubation time at the C-Stars formation temperature. The protective corona can be selectively displaced upon an addition of a DNA trigger, exposing the cholesterol molecules rich particle core and triggering membrane disruption, resulting in membrane rupture and cargo release. Aforementioned particles can be easily adapt via minor structure modifications to serve as a novel antimicrobial or bio-inspired drug delivery systems.

References

[1] Walczak, Michal, Ryan A. Brady, Leonardo Mancini, Roger Rubio-Sanchez, Claudia Contini, Will T. Kaufhold, Pietro Cicuta, and Lorenzo Di Michele. “Responsive Core-Shell DNA Particles Trigger Lipid-Membrane Rupture and Pathogen Entrapment.” Nature Communications, Under Review

[2] Brady, Ryan A., Nicholas J. Brooks, Pietro Cicuta, and Lorenzo Di Michele. “Crystallization of Amphiphilic DNA C-Stars.” Nano Letters 17, no. 5 (May 10, 2017): 3276–81. https://doi.org/10.1021/acs.nanolett.7b00980.

[3] Brady, Ryan A., Nicholas J. Brooks, Vito Foderà, Pietro Cicuta, and Lorenzo Di Michele. “Amphiphilic-DNA Platform for the Design of Crystalline Frameworks with Programmable Structure and Functionality.” Journal of the American Chemical Society 140, no. 45 (November 14, 2018): 15384–92. https://doi.org/10.1021/jacs.8b09143.

[4] Brady, Ryan A., Will T. Kaufhold, Nicholas J. Brooks, Vito Foderà, and Lorenzo Di Michele. “Flexibility Defines Structure in Crystals of Amphiphilic DNA Nanostars.” Journal of Physics: Condensed Matter 31, no. 7 (January 2, 2019): 074003. https://doi.org/10.1088/1361-648X/aaf4a1.