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A route to self-assembling DNA nano-complexes

The formulation of suspended nanoparticles is an essential step to multiple applications, such as designing therapeutic vectors, creating paints and microemulsions, or making multilayer surfaces. Polymers carrying electrical charges are most often the building blocks of such materials. Finding a route to form nano-aggregates that stay soluble requires a better understanding of the association process and in particular of the charges redistribution during the assembly.

Highly charged polyelectrolytes (polymers of high charge density) can self-assemble in presence of condensing agents such as multivalent cations, amphiphilic molecules or proteins of opposite charge. Aside precipitation, the formation of soluble micro- and nano-particles has been reported in multiple systems. However a precise control of experimental conditions needed to achieve the desired structures has been so far hampered by the extreme sensitivity of the samples to formulation pathways. Moreover, despite several theoretical as well as simulation studies focusing specifically on the formation of polyelectrolytes–multivalent ions complexes, the involved mechanisms remain mostly mysterious and need to be elucidated.

We focused on DNA because it is an extremely well controlled and widely investigated polymer with a high charge density that makes it an archetypal strong polyelectrolyte. Its condensation is directly relevant to genome packaging in vivo and to formulation of non-viral vectors for gene therapy. Small proteins named protamines, responsible for sperm chromatin condensation, have been chosen for their precise amino acid composition and high charge density. Protamines and short DNA fragments, being oppositely charged, attract each other and may assemble spontaneously into nano-particles of bundle shape. We have combined experiments and molecular modelling to investigate the detailed microscopic dynamics and the structure of the self-assembled hexagonal bundles. We demonstrate that the heterogeneities in composition induced by the experimental protocol play a crucial role in the formation and the stabilization of these nano-aggregates. Our results should help re-interpreting puzzling behaviors reported for a large class of strongly charged polyelectrolyte systems.

DNA nano-complexes assembled by small proteins (protamines) (right : imaged by electron cryomicroscopy showing a regular spacing ; left : results of molecular simulation). Color code : DNA (grey) and its monovalent cations (blue), protamines (red) and its monovalent anions (green).


A route to self-assemble suspended DNA nano-complexes
Yves Lansac, Jeril Degrouard, Madalena Renouard, Adriana C. Toma, Françoise Livolant & Eric Raspaud
Scientific Reports 6, 21995 (2016)


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