DNA condensation
DNA condensation refers to the process of compacting DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 molecules in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

or in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

. Mechanistic details of DNA packing are essential for its functioning in the process of gene regulation in living systems. Condensed DNA often has surprising properties, which one would not predict from classical concepts of dilute solutions. Therefore DNA condensation in vitro serves as a model system for many processes of physics
Physics is a natural science that involves the study of matter and its motion through spacetime, along with related concepts such as energy and force. More broadly, it is the general analysis of nature, conducted in order to understand how the universe behaves.Physics is one of the oldest academic...

, biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...

 and biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...

. In addition, DNA condensation has many potential applications in medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....

 and biotechnology
Biotechnology is a field of applied biology that involves the use of living organisms and bioprocesses in engineering, technology, medicine and other fields requiring bioproducts. Biotechnology also utilizes these products for manufacturing purpose...


DNA diameter is about 2 nm, while the length of a stretched single molecule may be up to several dozens of centimetres depending on the organism. Many features of the DNA double helix contribute to its large stiffness, including the mechanical properties of the sugar-phosphate backbone, electrostatic repulsion between phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

s (DNA bears on average one elementary negative charge per each 0.17 nm of the double helix), stacking interactions between the bases of each individual strand, and strand-strand interactions. DNA is one of the stiffest natural polymers, yet it is also one of the longest molecules. This means that at large distances DNA can be considered as a flexible rope, and on a short scale as a stiff rod. Like a garden hose, unpacked DNA would randomly occupy a much larger volume than when it is orderly packed. Mathematically, for a non-interacting flexible chain randomly diffusing in 3D, the end-to-end distance would scale as a square root of the polymer length. For real polymers such as DNA this gives only very rough estimate; what is important, is that the space available for the DNA in vivo is much smaller than the space that it would occupy in the case of a free diffusion in the solution. In order to cope with the volume constraints, DNA has a striking property to pack itself in the appropriate solution conditions with the help of ions and other molecules. Usually, DNA condensation is defined as "the collapse of extended DNA chains into compact, orderly particles containing only one or a few molecules". This definition applies to many situations in vitro and is also close to the definition of DNA condensation in bacteria as "adoption of relatively concentrated, compact state occupying a fraction of the volume available". In eukaryotes, the DNA size and the number of other participating players are much larger, and a DNA molecule forms millions of ordered nucleoprotein
A nucleoprotein is any protein that is structurally associated with nucleic acid .Many viruses harness this protein, and they are known for being host-specific...

 particles, the nucleosome
Nucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool....

s, which is just the first of many levels of DNA packing.

DNA condensation in viruses

In virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

es and bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...

s, the DNA or RNA is surrounded by a protein capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...

, sometimes further enveloped by a lipid membrane
-In biology:* Biological membrane* Cell membrane, a biological type of Membrane ** Inner membrane** Outer membrane * The two fetal membranes** amnion** chorion* Basement membrane* Mucous membrane* Serous membrane...

. Double-stranded DNA is stored inside the capsid in the form of a spool, which can have different types of coiling leading to different types of liquid-crystalline
Liquid crystal
Liquid crystals are a state of matter that have properties between those of a conventional liquid and those of a solid crystal. For instance, an LC may flow like a liquid, but its molecules may be oriented in a crystal-like way. There are many different types of LC phases, which can be...

 packing. This packing can change from hexagonal to cholesteric to isotropic at different stages of the phage functioning. Although the double helices are always locally aligned, the DNA inside viruses does not represent real liquid crystals, because it lacks fluidity. On the other hand, DNA condensed in vitro, e.g. with the help of polyamines which are also present in viruses, is both locally ordered and fluid.

DNA condensation in bacteria

Bacterial DNA is packed with the help of polyamines and proteins. Protein-associated DNA occupies about 1/4 of the intracellular volume forming a concentrated viscous phase with liquid crystalline properties, called the nucleoid. Similar DNA packaging exists also in chloroplast
Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...

s and mitochondria. Bacterial DNA is sometimes referred to as the bacterial chromosome. Bacterial nucleoid evolutionary represents an intermediate engineering solution between the protein-free DNA packing in viruses and protein-determined packing in eukaryotes.

DNA condensation in eukaryotes

Eukaryotic DNA with a typical length of dozens of centimeters should be orderly packed to be readily accessible inside the micrometer-size nucleus. In primitive unicellular eukaryotes such as dinoflagellates, it is possible to distinguish liquid-crystalline chromosomal ordering similar to bacterial chromosomes, just with higher DNA density. However, this is the only exception in the eukaryotic world. In other eukaryotes, DNA is arranged in the cell nucleus with the help of histones. In this case, the basic level of DNA compaction is the nucleosome, where the double helix is wrapped around the histone octamer containing two copies of each histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...

Histone H2A
Histone H2A is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N terminal tail, H2A is involved with the structure of the nucleosomes of the 'beads on a string' structure.Other histone proteins...

, H2B
Histone H2B
Histone H2B is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N terminal tail H2B is involved with the structure of the nucleosomes of the 'beads on a string' structure.See nucleosome, histone and...

, H3
Histone H3
Histone H3 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a string' structure...

 and H4
Histone H4
Histone H4 is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N terminal tail, H4 is a structural component of the nucleosome, and is subject to covalent modification, including acetylation and methylation,...

. Linker histone H1
Histone H1
Histone H1 is one of the five main histone protein families which are components of chromatin in eukaryotic cells. Though highly conserved, it is nevertheless the most variable histone in sequence across species.- Structure :...

 binds the DNA between nucleosomes and facilitates packaging of the 10 nm "beads on the string" nucleosomal chain into a more condensed 30 nm fiber. Most of the time, between cell divisions, chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

 is optimized to allow easy access of transcription factors to active genes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...

, which are characterized by a less compact structure called euchromatin
Euchromatin is a lightly packed form of chromatin that is rich in gene concentration, and is often under active transcription. Unlike heterochromatin, it is found in both cells with nuclei and cells without nuclei...

, and to alleviate protein access in more tightly packed regions called heterochromatin
Heterochromatin is a tightly packed form of DNA, which comes in different varieties. These varieties lie on a continuum between the two extremes of constitutive and facultative heterochromatin...

. During the cell division, chromatin compaction increases even more to form chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

s, which can cope with large mechanical forces dragging them into each of the two daughter cells.

DNA condensation in vitro

DNA condensation can be induced in vitro either by applying external force to bring the double helices together, or by inducing attractive interactions between the DNA segments. The former can be achieved e.g. with the help of the osmotic pressure exerted by crowding neutral polymersin the presence of monovalent salts. In this case, the forces pushing the double helices together are coming from entropic random collisions with the crowding polymers surrounding DNA condensates, and salt is required to neutralize DNA charges and decrease DNA-DNA repulsion. The second possibility can be realized by inducing attractive interactions between the DNA segments by multivalent cationic charged ligands (multivalent metal ions, inorganic cations, polyamines, protamines, peptides, lipids, liposomes and proteins.

Physics of DNA condensation

Condensation of long double-helical DNAs is a sharp phase transition
Phase transition
A phase transition is the transformation of a thermodynamic system from one phase or state of matter to another.A phase of a thermodynamic system and the states of matter have uniform physical properties....

, which takes place within a narrow interval of condensing agent concentrations.[ref] Since the double helices come very closely to each other in the condensed phase, this leads to the restructuring of water molecules, which gives rise to the so called hydration forces.[ref] In order to understand attraction between negatively charged DNA molecules, one also has to take into account correlations between counterions in the solution.[ref]

DNA condensation and gene regulation

Most nowadays descriptions of gene regulation are based on the approximations of equilibrium binding in dilute solutions, although it is clear that these assumptions are in fact violated in chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

. The dilute-solution approximation is violated for two reasons. First, the chromatin content is far from being dilute, and second, the numbers of the participating molecules are sometimes so small, that it does not make sense to talk about the bulk concentrations. Further differences from dilute solutions arise due to the different binding affinities of proteins to condensed and uncondensed DNA. Thus in condensed DNA both the reaction rates can be changed and their dependence on the concentrations of reactants may become nonlinear.

Further reading

  • Gelbart, W. M., R. Bruinsma, P. A. Pincus, and V. A. Parsegian. 2000. DNA-Inspired Electrostatics. Physics Today 53:38.
  • Strey, H. H., R. Podgornik, D. C. Rau, and V. A. Parsegian. 1998. DNA-DNA interactions. Curr Opin Struct Biol 8:309-313.
  • Schiessel, H. 2003. The physics of chromatin. J. Physics: Cond. Mat. 15:R699-R774.
  • Vijayanathan, V., T. Thomas, and T. J. Thomas. 2002. DNA nanoparticles and development of DNA delivery vehicles for gene therapy. Biochemistry 41:14085-14094.
  • Yoshikawa, K. 2001. Controlling the higher-order structure of giant DNA molecules Advanced Drug Delivery Reviews 52:235-244
  • Hud, N. V., and I. D. Vilfan. 2005. Toroidal DNA condensates: unraveling the fine structure and the role of nucleation in determining size. Annu Rev Biophys Biomol Struct 34:295-318.
  • Yoshikawa, K., and Y. Yoshikawa. 2002. Compaction and condensation of DNA. In Pharmaceutical perspectives of nucleic acid-based therapeutics. R. I. Mahato, and S. W. Kim, editors. Taylor & Francis. 137-163.
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