Monte Carlo studies on polyelectrolyte complexes

Structural properties and topology of polyelectrolyte complexes

Structural properties and the topology of polyelectrolyte complexes formed by a long polyion and shorter and oppositely charged polyions of varying length in solution have been investigated under different conditions by Monte Carlo simulations using a coarse-grained model. The extension of individual polyions has been characterized by their radius of gyration, whereas the composition and the internal topological structure of the complexes by their net charge and a novel analysis describing how the shorter polycations link to monomers of the longer polyanion. Conditions have been found at which the polyanion and a given number of polycations form distinguishable complexes differing in (i) the polyanion conformation and (ii) the fraction of polycations being in extended and collapsed states. Thus, at equilibrium these polyelectrolyte complexes display a stepwise variation of the degree of intracomplex disproportionation of the polycations, also referred to as a intrachain segregation, in agreement with previous theoretical predictions. The coexistence of different polyelectrolyte complex structures appeared, generally, at mixing ratios close to but different from charge equivalence. A broad polyanion size distribution and a bimodal polycation size distribution appeared as a consequence of the coexistence of different polyelectrolyte complex structures.

People: Rita Dias, Per Linse (Univ. Lund, Sweden) and Alberto Pais (Univ. Coimbra, Portugal)

References:

• Stepwise disproportionation in polyelectrolyte complexes.
  Dias, R.S.; Linse, P.; Pais, A.A.C.C.
  J Comp Chem 12 (2011) 2697-2707.

Polyelectrolyte compaction by pH-responsive agents

Compaction of negatively charged polyanions by polycations with different characteristics is investigated using Monte Carlo simulation in a coarse-grain model. Two different routes are tested and the results compared. In one, the polycation/polyanion charge ratio is varied by increasing the amount of polycations, keeping all the chain characteristics constant. In the other, the linear charge density of the polycations is altered but their number is kept constant. The set of systems in which the linear charge density changes is used as a model for a system comprising chains with different degrees of ionization under different pH conditions. In both cases, polycation/polyanion charge ratios ranging from 0.25 to 1.25 are addressed. The system with unitary charge ratio is common to both routes. It is seen that, although the overall trends followed by the two sets of systems are similar, marked differences can be discerned both for low charge ratios, and for the higher ones, where the systems are overcharged. Coexistence regimes are clearly detected in some of the systems. Using route one produces, generally, more compact structures, irrespective of the charge ratio. These are accompanied by narrower distributions. We note that most experimental applications benefit from a monodisperse population of complexes. Also, the absolute charge is of paramount importance. If undercharged complexes are more desirable for the application in question, then using fewer polycations with higher density, i.e. lower pH values, leads to slightly less polydisperse complexes and more compact structures. For applications where overcharged complexes are required, there are two possibilities, according to what is required. Polyplexes prepared at lower pH values are more expanded and polydisperse. At higher pH values, the polyanion is generally more compact and the excess charge is accommodated in the form of tails protruding from the complex. We speculate that these complexes are the most appropriate for gene delivery since the “positive tails” would act to electrostatically stabilize the complex, avoiding aggregation and precipitation , and facilitating the approach to the cell membranes . The size would be sufficiently small to overcome the cell membrane and yet sufficiently expanded to allow the access of DNA to the cell machinery, in what is presumably a very favorable situation for gene delivery into cells .

People: Rita Dias, Andreia Jorge and Alberto Pais (Univ. Coimbra, Portugal)

References:

• Polyelectrolyte compaction by pH-responsive agents
  Jorge, A.F.; Sarraguca, J.M.G; Dias, R.S.; Pais, A.A.C.C.
  Phys Chem Chem Phys 09 (2009) 10890-10898.

Enhanced condensation and facilitated release of DNA using mixed cationic agents

Efficient DNA condensation and decondensation, as well as low toxicity, are required for an efficient gene delivery vehicle. In this work we report on the condensation of DNA by a mixture of cationic agents, low-molecular-weight polyethylenimine (PEI, 1.2 KDa) and Fe(III) ions, and respective decondensation, using experimental and theoretical methods. It was found that a significant reduction in the amount of PEI necessary to induce DNA condensation is achieved by the addition of the trivalent ions, which are very inefficient on their own. In addition, the mixture makes DNA decompaction by heparin easier, starting from similar degrees of condensation. The results obtained using simulations of coarse-grain models are coherent with those obtained experimentally. It was also found that the improved effect of the multivalent ions is related to the preferred positioning of the trivalent ions in the DNA areas less populated by the polycation chains, in between the polycation chains and at the ends of the DNA, which facilitates the overall condensation.

People: Rita Dias, Andreia Jorge and Alberto Pais (Univ. Coimbra, Portugal)

References:

• Enhanced Condensation and Facilitated Release of DNA Using Mixed Cationic Agents: A Combined Experimental and Monte Carlo Study.
  Jorge, A.F.; Dias, R.S.; Pais, A.A.C.C.
  Biomacromolecules 13 (2012) 3151-3161.