Effect of nanochannel geometry on DNA structure in the presence of macromolecular crowding agent

Jones, van der Maarel, and Doyle experimentally and numerically study the effects of macromolecular crowding agents on DNA structure when confined to a nanochannel. Curiously, DNA response to crowding is significantly different between bulk phase, nanoslit, and nanotube confinement. Coarse grained Brownian dynamics simulations reproduce trends seen in the experiments and allow us to develop a deeper understanding of the key physics at play in these systems. It is proposed that the occupancy of free volume next to the channel wall by crowders causes an effective reduction in confining dimensions of the channel that initially swells DNA in nanoconfinement. This work has been done in collaboration with SMART BioSyM. Nano Letters (2011).

Control of the flow properties of DNA by topoisomerase II and its targeting inhibitor

DNA tangles and forms an elastic gel once the concentration exceeds a certain critical value. A test molecule (magenta) can only move in a snakelike fashion along the axial line of a tube of confinement (white), because lateral displacements are prohibited by entanglements (asterisks) with other molecules (blue). The density of entanglements and the molecular relaxation times determine the properties of the flow. Topoisomerase II is expected to play an essential role in DNA rheology, due to the removal of entanglements by the catalyzed double strand passage reaction. To test this conjecture, Kundukad and van der Maarel measured the elastic storage and viscous loss moduli of a model system composed of bacteriophage Lambda-DNA and human topoisomerase IIalpha. They observed that topoisomerase II indeed untangles DNA and transforms an initially entangled solution from an elastic gel to a viscous fluid depending on the consumption of ATP. Another aspect of their study is the effect of adenylyl-imidodiphosphate as a generic example of a topoisomerase II targeting anticancer drug. Biophysical Journal 99, 1906-1915 (2010).

Macromolecular crowding induced elongation and compaction of single DNA molecules confined in a nanochannel

The effect of dextran nanoparticles on the conformation and compaction of single DNA molecules confined in a nanochannel was investigated with fluorescence microscopy. It was observed that the molecules elongate and eventually condense into a compact form with increasing volume fraction of the crowding agent. In crowded condition, the channel diameter is effectively reduced, which is interpreted in terms of depletion in DNA segment density in the interfacial region next to the channel wall. Confinement in a nanochannel also facilitates compaction with a neutral crowding agent at low ionic strength. The threshold volume fraction for condensation is proportional to the size of the nanoparticle, due to depletion induced attraction between DNA segments. Zhang, Shao, van Kan, and van der Maarel found that the effect of crowding is not only related to the colligative properties of the agent and that confinement is also important. Proceedings of the National Academy of Sciences of the United States of America 106, 16651-16656 (2009).

Molecular dynamics simulation of multivalent-ion mediated attraction between DNA molecules

Molecular dynamics simulations were done to study the interaction between two parallel double-stranded DNA molecules in the presence of the multivalent putrescine (2+), spermidine (3+), spermine (4+) or cobalt hexamine (3+). The attractive force is rationalized in terms of the formation of ion bridges, i.e., multivalent ions which are simultaneously bound to the two opposing DNA molecules. The lifetime of the ion bridges is short on the order of a few nanoseconds. Physical Review Letters 100, 118310 (2008).