Aggregation of strongly‐charged polymers (polyelectrolytes) has been extensively studied due to its importance in biological phenomena such as DNA packaging, gene regulation, and cytoskeleton organization. DNA has been one of the most studied strong polyelectrolyte and it has been shown that it can condense in vitro into various morphologies under a large variety of agents such as multivalent cations, poly-ions and basic proteins. Such effective attraction between like-charged polyelectrolytes is occurring for other semiflexible polyelectrolytes, indicating that specific interactions are not the main driving force. Instead, the short-range attraction has been theoretically ascribed to a certain form of positional correlations of the oppositely‐charged agents adsorbed along the polyelectrolyte chains.
Protamines are highly charged proteins compacting efficiently DNA during the spermatogenesis process. They are also used as non-toxic gene carriers for therapy purposes. Using salmon proteins (+21e) and short DNA fragments (146 bp), we have explored the physico-chemical conditions required for protamines to condense DNA. At low salt concentration, a set of experiments combining electrophoresis, light scattering and cryoelectron microscopy reveals the existence of small charged DNA–protamine complexes coexisting either with DNA or protamines in solution. We have used a coarse-grained model capturing the main molecular characteristics of DNAs and proteins and integrating out the atomistic degrees of freedom in order to probe larger timescale and length scale. Molecular dynamics and Langevin dynamics have been performed to explore the self-assembly phenomena. Aggregation is controlled solely by strong electrostatic interactions and spatial inhomogeneities introduced by the experimental protocol coupled to an order of magnitude difference in diffusion coefficients between DNA and proteins could play a crucial role in the self-assembly.
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