not cause DNA compaction, which is the collapse of DNA into a compact structure.
The compaction of DNA by an incompatible polymer has been modeled as a
coil–globule transition such as observed in other polymers [60], and is also the
topic of recent studies by the group of Dias, Lindman and colleagues [61, 62].
What seems to be the predominant method for polyplex formation is the addition
of a polymer solution to a DNA solution. Some of the consequences of this
procedure are that the concentration of the DNA solution changes in course of the
addition (increase in volume) and DNA is consumed by the ongoing complexation
process. Despite the importance of the addition rate, it is often not mentioned in
polyplex studies. For instance, from IPEC studies it was found that the higher the
titrant addition rate, the higher the storage stability of the complexes in the case of
random copolymers of sodium 2-acrylamido-2-methylpropanesulfonate with either
t-butyl acrylamide or methyl methacrylate complexed with poly(diallyldimethylammonium chloride) or with an ionene-type polycation containing 95 mol% N,Ndimethyl-2-hydroxypropyleneammonium chloride repeat units [63]. Moreover, by
addition of a polycation to DNA, the zeta potential increases from negative values
(DNA) to positive values (nanoparticles with excess of polycations).
The behavior of both DNA and polyplexes is also a function of the starting
concentration of DNA, which can be in the dilute (polymers act as individual units
without intermolecular interactions), intermediate, or semi-dilute regime (polymer
chains overlap each other and form a transient network). IPEC studies of the
complexation of poly(allylamine hydrochloride) and the two polyanions poly
(acrylic acid) and poly(methacrylic acid) have shown that the higher the concentration, the larger and denser are the complexes formed [64]. Unfortunately, this type
of study with complexes of DNA and polycations are still scarce.
Structural Models
Two structural models are discussed in the literature for polyelectrolyte complex
(PEC) formation, depending on the components (weak or strong polyelectrolyte,
stoichiometry, molecular weight) and the external conditions (presence of salts,
etc.): ladder-like (complex formation takes place on a molecular level via conformational adaptation) or “scrambled egg” structure (large number of chains in a
particle) (Scheme 5) [65].
The ladder-like structure results from the mixing of polyelectrolytes having
weak ionic groups and large differences in molecular dimensions. It is the result
of the propagation of the complex reaction as a “zippering action,” since the ionic
sites next to the first reacted ones would be the most likely to react next. The
“scrambled egg” structure refers to complexes that are the product of the combination of polyelectrolytes having strong ionic groups and comparable molecular
dimensions. These models have been extensively discussed and most experimental
structures lie between these two models, though probably closer to the scrambled
egg than the ladder model [66], especially in the case of complexes of DNA with
polycations.
114
A. Bertin
The compaction of DNA by an incompatible polymer has been modeled as a
coil–globule transition such as observed in other polymers [60], and is also the
topic of recent studies by the group of Dias, Lindman and colleagues [61, 62].
What seems to be the predominant method for polyplex formation is the addition
of a polymer solution to a DNA solution. Some of the consequences of this
procedure are that the concentration of the DNA solution changes in course of the
addition (increase in volume) and DNA is consumed by the ongoing complexation
process. Despite the importance of the addition rate, it is often not mentioned in
polyplex studies. For instance, from IPEC studies it was found that the higher the
titrant addition rate, the higher the storage stability of the complexes in the case of
random copolymers of sodium 2-acrylamido-2-methylpropanesulfonate with either
t-butyl acrylamide or methyl methacrylate complexed with poly(diallyldimethylammonium chloride) or with an ionene-type polycation containing 95 mol% N,Ndimethyl-2-hydroxypropyleneammonium chloride repeat units [63]. Moreover, by
addition of a polycation to DNA, the zeta potential increases from negative values
(DNA) to positive values (nanoparticles with excess of polycations).
The behavior of both DNA and polyplexes is also a function of the starting
concentration of DNA, which can be in the dilute (polymers act as individual units
without intermolecular interactions), intermediate, or semi-dilute regime (polymer
chains overlap each other and form a transient network). IPEC studies of the
complexation of poly(allylamine hydrochloride) and the two polyanions poly
(acrylic acid) and poly(methacrylic acid) have shown that the higher the concentration, the larger and denser are the complexes formed [64]. Unfortunately, this type
of study with complexes of DNA and polycations are still scarce.
Structural Models
Two structural models are discussed in the literature for polyelectrolyte complex
(PEC) formation, depending on the components (weak or strong polyelectrolyte,
stoichiometry, molecular weight) and the external conditions (presence of salts,
etc.): ladder-like (complex formation takes place on a molecular level via conformational adaptation) or “scrambled egg” structure (large number of chains in a
particle) (Scheme 5) [65].
The ladder-like structure results from the mixing of polyelectrolytes having
weak ionic groups and large differences in molecular dimensions. It is the result
of the propagation of the complex reaction as a “zippering action,” since the ionic
sites next to the first reacted ones would be the most likely to react next. The
“scrambled egg” structure refers to complexes that are the product of the combination of polyelectrolytes having strong ionic groups and comparable molecular
dimensions. These models have been extensively discussed and most experimental
structures lie between these two models, though probably closer to the scrambled
egg than the ladder model [66], especially in the case of complexes of DNA with
polycations.
114
A. Bertin