Condensation of DNA using poly(amido amine) dendrimers: effect of salt concentration on aggregate morphology

Carnerup, Anna M.; Ainalem, Marie-Louise; Alfredsson, Viveka; Nylander, Tommy

doi:10.1039/c0sm00644k

Cited by 32 publications

(41 citation statements)

References 36 publications

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“…The nucleation occurs in the equilibrium between association and dissociation ( Figure 2). Once a nucleation site forms and is energetically favorable, the growth process proceeds through the incorporation of surrounding polyplexes to ultimately form rod-shaped or toroidal structures containing multimolecules of DNA [35][36][37]. The kinetics of the structure formation has been investigated in hexammine cobalt-based polyplexes.…”

Section: Dna Condensation Induced By Low-or High-molecular-weight Polmentioning

confidence: 99%

Structural Polymorphism of Single pDNA Condensates Elicited by Cationic Block Polyelectrolytes

Osada

2020

Polymers

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DNA folding is a core phenomenon in genome packaging within a nucleus. Such a phenomenon is induced by polyelectrolyte complexation between anionic DNA and cationic proteins of histones. In this regard, complexes formed between DNA and cationic polyelectrolytes have been investigated as models to gain insight into genome packaging. Upon complexation, DNA undergoes folding to reduce its occupied volume, which often results in multi-complex associated aggregates. However, when cationic copolymers comprising a polycation block and a neutral hydrophilic polymer block are used instead, DNA undergoes folding as a single molecule within a spontaneously formed polyplex micelle (PM), thereby allowing the observation of the higher-order structures that DNA forms. The DNA complex forms polymorphic structures, including globular, rod-shaped, and ring-shaped (toroidal) structures. This review focuses on the polymorphism of DNA, particularly, to elucidate when, how, and why DNA organizes into these structures with cationic copolymers. The interactions between DNA and the copolymers, and the specific nature of DNA in rigidity; i.e., rigid but foldable, play significant roles in the observed polymorphism. Moreover, PMs serve as potential gene vectors for systemic application. The significance of the controlled DNA folding for such an application is addressed briefly in the last part.

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Section: Dna Condensation Induced By Low-or High-molecular-weight Polmentioning

confidence: 99%

Structural Polymorphism of Single pDNA Condensates Elicited by Cationic Block Polyelectrolytes

Osada

2020

Polymers

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“…Let us mention for example hexagonal polymer-cationic surfactant complexes 1 2 , hollow icosahedron made of catanionic surfactants 3 , DNA-dendrimers or DNA-lipopolyamines complexes 4 5 6 . Such nano-aggregates have been often obtained with biological components and their structure has been explored (see for example 7 8 9 10 ). Their defined size and charge are of utmost importance for many purposes in diverse fields of applications ranging from cosmetics or gene-therapy to paintings, waste-water treatment or paper industry 11 .…”

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confidence: 99%

A route to self-assemble suspended DNA nano-complexes

Lansac

Degrouard

Renouard

et al. 2016

Sci Rep

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Highly charged polyelectrolytes 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. Herein we combine experiments and molecular modelling to investigate the detailed microscopic dynamics and the structure of self-assembled hexagonal bundles made of short dsDNA fragments complexed with small basic proteins. We suggest that inhomogeneous mixing conditions are required to form and stabilize charged self-assembled nano-aggregates in large excess of DNA. Our results should help re-interpreting puzzling behaviors reported for a large class of strongly charged polyelectrolyte systems.

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“…Besides, the charge density of the electrostatic screening layer increases sharply with the increase of salt concentration, which greatly weakens the electrostatic attraction between the ssDNA and dendrimer, hence causing poor binding affinity. Using cryo‐TEM, Carnerup et al observed that for the lower generation PAMAM dendrimers (G1, G2, and G4), an increase in aggregate size occurred as a result of higher salt concentrations. This experimental observation agrees qualitatively with our DPD calculations, where R g values of ssDNA–G4 PAMAM complexes increase monotonically when salt concentration is increased.…”

Section: Resultsmentioning

confidence: 99%

“…It was indicated that the transfection efficiency of nucleic acid–dendrimer complexes is directly correlated with their particle structure and size . Recently, extensive experimental studies have been performed to investigate the size and morphology of complexes formed by cationic PAMAM dendrimers and nucleic acids . For example, Ainalem and Nylander observed a rich variety of morphologies of DNA–dendrimer complexes using cryo‐TEM, which depends on the size and charge of the dendrimer, and the salt concentration of the aqueous solution significantly.…”

Section: Introductionmentioning

confidence: 99%

“…[19] Recently, extensive experimental studies have been performed to investigate the size and morphology of complexes formed by cationic PAMAM dendrimers and nucleic acids. [20][21][22][23][24] For example, Ainalem and Nylander [23] observed a rich variety of morphologies of DNA-dendrimer complexes using cryo-TEM, which depends on the size and charge of the dendrimer, and the salt concentration of the aqueous solution significantly. Through atomic force microscopy, Shen et al [24] demonstrated that effective construction of stable nanoscale and uniform RNA-dendrimer complexes depends critically on the size of the RNA molecule, the dendrimer generation, and the charge ratio between the dendrimer and the RNA.…”

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Computer Simulation of DNA Condensation by PAMAM Dendrimer

Quan

et al. 2018

Macro Theory & Simulations

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In this study, dissipative particle dynamics is employed to investigate the complexation of poly(amido amine) dendrimer and single‐stranded DNA (ssDNA). A coarse‐grained model for ssDNA is constructed, which reproduces correctly the conformational behavior of the ssDNA molecules. The effects of pH, dendrimer generation, ionic strength, and dendrimer/ssDNA charge ratio on DNA–dendrimer complexes are explored. Simulation results show that ssDNA molecules can be significantly condensed by dendrimers and stable complexes are obtained by regulating the pH value. The ssDNA chain penetration would complicate its release from dendrimer, while this can be tuned by different generations of dendrimer. Salt concentration affects the size and stability of the complexes through ion screening effect. Dendrimer/ssDNA charge ratio can be used to control the size and morphology of the complex. This work can help design dendrimer‐based gene vectors.

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Condensation of DNA using poly(amido amine) dendrimers: effect of salt concentration on aggregate morphology

Cited by 32 publications

References 36 publications

Structural Polymorphism of Single pDNA Condensates Elicited by Cationic Block Polyelectrolytes

Structural Polymorphism of Single pDNA Condensates Elicited by Cationic Block Polyelectrolytes

A route to self-assemble suspended DNA nano-complexes

Computer Simulation of DNA Condensation by PAMAM Dendrimer

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