We present extensive molecular dynamics simulations of a cationic nanoparticle and a double-stranded DNA molecule to discuss the effect of DNA flexibility on the complex formation of a cationic nanoparticle with double-stranded DNA. Martini coarse-grained models were employed to describe double-stranded DNA molecules with two different flexibilities and cationic nanoparticles with three different electric charges. As the electric charge of a cationic nanoparticle increases, the degree of DNA bending increases, eventually leading to the wrapping of DNA around the nanoparticle at high electric charges. However, a small increase in the persistence length of DNA by 10 nm requires a cationic nanoparticle with a markedly increased electric charge to bend and wrap DNA around. Thus, a more flexible DNA molecule bends and wraps around a cationic nanoparticle with an intermediate electric charge, whereas a less flexible DNA molecule binds to a nanoparticle with the same electric charge without notable bending. This work provides solid evidence that a small difference in DNA flexibility (as small as 10 nm in persistence length) has a substantial influence on the complex formation of DNA with proteins from a biological perspective and suggests that the variation of sequence-dependent DNA flexibility can be utilized in DNA nanotechnology as a new tool to manipulate the structure of DNA molecules mediated by nanoparticle binding.
Sequence-dependent coupling between DNA bending and its helical twist in DNA minicircles.
Sharp increase in macromolecular crowding induces abnormal chromatin compaction in the cell nucleus, suggesting its non-negligible impact on chromatin structure and function. However, the details of the crowding-induced chromatin compaction remain poorly understood. In this work, we present a computer simulation study on the entropic effect of macromolecular crowding on the interaction between chromatin structural units called nucleosome clutches. Nucleosome clutches were modeled by a chain of nucleosomes collapsed by harmonic restraints implicitly mimicking the nucleosome association mediated by histone tails and linker histones. The nucleosome density of the clutches was set close to either that of high-density heterochromatin or that of low-density euchromatin. The effective interactions between these nucleosome clutches were calculated in various crowding conditions, and it was found that the increase in the degree of macromolecular crowding induced attractive interaction between two clutches with high nucleosome density. Interestingly, the increased degree of macromolecular crowding did not induce any attraction between two clutches with low nucleosome density. Our results suggest that the entropic effect of macromolecular crowding can enhance binding between nucleosome clutches in heterochromatin, but not in euchromatin, as a result of the difference in nucleosome packing degrees.
We investigate the influence of macromolecular crowding on interactions between collapsed polymers using computer simulations, to gain insights into biomacromolecular interactions in crowded biological environments. The effective attraction is induced between two collapsed polymers due to the macromolecular crowding, and it is found that the strength of the effective attraction decreases as the crowder size is reduced for a fixed crowder volume fraction, which is sharply contrasted with the conventional viewpoint based on the depletion attraction observed for hard-core spherical colloids. This unusual trend of size-dependence is interpreted by dividing the effective interaction into the polymer-mediated repulsion and crowder-mediated attraction. It is found that the ranges of repulsive and attractive contributions overlap significantly due to the flexible nature of polymer boundaries, resulting in partial cancellation over this range which leads to the observed size-dependence. Thus, this work suggests that the effective interactions between biomacromolecules in crowded environments may be qualitatively different from the depletion interactions predicted for hard-core spherical colloids.
Phase separation in a biological cell nucleus occurs in a heterogeneous environment filled with a high density of chromatins and thus it is inevitably influenced by interactions with chromatins. As a model system of nuclear body formation in a cell nucleus filled with chromatins, we simulate the phase separation of a low-density Lennard-Jones (LJ) fluid interacting with a long, condensed polymer chain. The influence of the density variation of LJ particles above and below the phase boundary and the role of attractive interactions between LJ particles and polymer segments are investigated at a fixed value of strong self-interaction between LJ particles. For a density of LJ particles above the phase boundary, phase separation occurs and a dense domain of LJ particles forms irrespective of interactions with the condensed polymer chain whereas its localization relative to the polymer chain is determined by the LJ-polymer attraction strength. Especially, in the case of moderately weak attractions, the domain forms separately from the polymer chain and subsequently associates with the polymer chain. When the density is below the phase boundary, however, the formation of a dense domain is possible only when the LJ-polymer attraction is strong enough, for which the domain grows in direct contact with the interacting polymer chain. In this work, different growth behaviors of LJ particles result from the differences in the density of LJ particles and in the LJ-polymer interaction, and this work suggests that the distinct formation of activity-dependent and activity-independent nuclear bodies (NBs) in a cell nucleus may originate from the differences in the concentrations of body-specific NB components and in their interaction with chromatins.
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