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Biophys. J. BioFAST: First Published January 14, 2005. doi:10.1529/biophysj.104.052100
© 2005 by the Biophysical Society.


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SUPRAMOLECULAR ASSEMBLIES

Contribution of hydrophobicity to thermodynamics of ligand-DNA binding and DNA collapse

Mayank M. Patel 1* and Thomas J. Anchordoquy 1

1 University of Colorado Health Sciences Center

* To whom correspondence should be addressed. E-mail: mayank.patel{at}uchsc.edu.

Submitted on August 31, 2004
Revised on October 7, 2004
Accepted on 30 November 2004


   Abstract
The importance of understanding the dynamics of DNA condensation is inherent in the biological significance of DNA packaging in cell nuclei, as well as for gene therapy applications. Specifically, the role of ligand hydrophobicity in DNA condensation has received little attention. Considering that only multivalent cations can induce true DNA condensation, previous studies exploring monovalent lipids have been unable to address this question. In this study we have elucidated the contribution of the hydrophobic effect to multivalent cation- and cationic lipid-DNA binding and DNA collapse by studying the thermodynamics of cobalt hexammine-, spermine- and lipospermine-plasmid DNA binding at different temperatures. Comparable heat capacity changes ({Delta}Cp) associated with cobalt hexammine- and spermine-DNA binding (-23.39 cal/mol K and -17.98 cal/mol K, respectively) suggest that upon binding to DNA there are insignificant changes in the hydration state of the methylene groups in spermine. In contrast, the acyl chain contribution to the {Delta}Cp of lipospermine-DNA binding ({Delta}Cp {varphi} = {Delta}Cp lipospermine - {Delta}Cp spermine) is significant (-220.94 cal/mol K). Although lipopermine induces DNA ordering into 'tubular' suprastructures, such structures do not assume toroidal dimensions as formed by spermine-DNA complexes. We postulate that a steric barrier posed by the acyl chains in the multivalent cationic lipid lipospermine precludes packaging of DNA into toroidal dimensions comparable to those found in nature.

Key Words: DNA condensation/collapse, DNA packaging, Energetics of polyamine- and cationic lipid-DNA binding, Isothermal Titration Calorimetry, Toroids




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Copyright © 2005 by the Biophysical Society.