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Biomedical subjects

E Maltsev

Publications and source records attributed to E Maltsev.

2 recordsLinked to original sources

DNA charge neutralization by linear polymers. II. Reversible binding.

We model the way in which polymers bind to DNA and neutralize its charged backbone by analyzing the dynamics of the distribution of gaps along the DNA. We generalize existing theory for irreversible binding to construct deterministic models which include polymer removal, movement along the DNA, and allow for binding with overlaps. We show that reversible binding alters the capacity of the DNA for polymers by allowing the rearrangement of polymer positions over a longer time scale than when binding is irreversible. When the polymers do not overlap, allowing reversible binding increases the number of polymers adhered and hence the charge that the DNA can accommodate; in contrast, when overlaps occur, reversible binding reduces the amount of charge neutralized by the polymers.

Binding Sites↗

DNA charge neutralization by linear polymers: irreversible binding.

We develop a deterministic mathematical model to describe the way in which polymers bind to DNA by considering the dynamics of the gap distribution that forms when polymers bind to a DNA plasmid. In so doing, we generalize existing theory to account for overlaps and binding cooperativity whereby the polymer binding rate depends on the size of the overlap. The proposed mean-field models are then solved using a combination of numerical and asymptotic methods. We find that overlaps lead to higher coverage and hence higher charge neutralizations, results which are more in line with recent experimental observations. Our work has applications to gene therapy where polymers are used to neutralize the negative charges of the DNA phosphate backbone, allowing condensation prior to delivery into the nucleus of an abnormal cell.

Binding Sites↗