The self-assembly of block polymers into well-ordered nanostructures underpins their utility across fundamental and applied polymer science, yet only a handful of equilibrium morphologies are known with the simplest AB-type materials. Here, we report the discovery of the A15 sphere phase in single-component diblock copolymer melts comprising poly(dodecyl acrylate)−block−poly(lactide). A systematic exploration of phase space revealed that A15 forms across a substantial range of minority lactide block volume fractions (fL = 0.25 − 0.33) situated between the σ-sphere phase and hexagonally close-packed cylinders. Self-consistent field theory rationalizes the thermodynamic stability of A15 as a consequence of extreme conformational asymmetry. The experimentally observed A15−disorder phase transition is not captured using mean-field approximations but instead arises due to composition fluctuations as evidenced by fully fluctuating field-theoretic simulations. This combination of experiments and field-theoretic simulations provides rational design rules that can be used to generate unique, polymer-based mesophases through self-assembly.
The interaction of DNA with proteins occurs over a wide range of length scales, and depends critically on its local structure. In particular, recent experimental work suggests that the intrinsic curvature of DNA plays a significant role on its protein-binding properties. In this work, we present a coarse grained model of DNA that is capable of describing base-pairing, hybridization, major and minor groove widths, and local curvature. The model represents an extension of the recently proposed 3SPN.2 description of DNA [D. M. Hinckley, G. S. Freeman, J. K. Whitmer, and J. J. de Pablo, J. Chem. Phys. 139, 144903 (2013)], into which sequence-dependent shape and mechanical properties are incorporated. The proposed model is validated against experimental data including melting temperatures, local flexibilities, dsDNA persistence lengths, and minor groove width profiles.
Nucleosomes provide the basic unit of compaction in eukaryotic genomes, and the mechanisms that dictate their position at specific locations along a DNA sequence are of central importance to genetics. In this Letter, we employ molecular models of DNA and proteins to elucidate various aspects of nucleosome positioning. In particular, we show how DNA's histone affinity is encoded in its sequence-dependent shape, including subtle deviations from the ideal straight B-DNA form and local variations of minor groove width. By relying on high-precision simulations of the free energy of nucleosome complexes, we also demonstrate that, depending on DNA's intrinsic curvature, histone binding can be dominated by bending interactions or electrostatic interactions. More generally, the results presented here explain how sequence, manifested as the shape of the DNA molecule, dominates molecular recognition in the problem of nucleosome positioning.
Nucleosomes represent the basic building block of chromatin and provide an important mechanism by which cellular processes are controlled. The locations of nucleosomes across the genome are not random but instead depend on both the underlying DNA sequence and the dynamic action of other proteins within the nucleus. These processes are central to cellular function, and the molecular details of the interplay between DNA sequence and nucleosome dynamics remain poorly understood. In this work, we investigate this interplay in detail by relying on a molecular model, which permits development of a comprehensive picture of the underlying free energy surfaces and the corresponding dynamics of nucleosome repositioning. The mechanism of nucleosome repositioning is shown to be strongly linked to DNA sequence and directly related to the binding energy of a given DNA sequence to the histone core. It is also demonstrated that chromatin remodelers can override DNA-sequence preferences by exerting torque, and the histone H4 tail is then identified as a key component by which DNA-sequence, histone modifications, and chromatin remodelers could in fact be coupled.nucleosome repositioning | chromatin dynamics | molecular simulation | advanced sampling techniques T he basic building block of eukaryotic chromatin is the nucleosome, a DNA-protein complex containing 147 bp of DNA wrapped around a disk-like protein complex known as the histone octamer (1). Since nucleosomal DNA is inaccessible to other DNA-binding proteins, such as transcription factors and polymerases (2-4), the locations of nucleosomes represent an important mechanism by which cellular processes are controlled. Notably, nucleosome positions are dynamic, with changes in transcription levels, cellular state, and environmental factors resulting in different packagings of chromatin (5, 6). Proper packaging of genomic DNA is critical to cellular function, and a wide range of human diseases have been associated with defects in chromatin structure (7,8). Understanding the molecular factors that control the locations of nucleosomes, and how they are dynamically modulated, therefore represents a central goal of molecular biology and biophysics.It is now appreciated that the DNA sequence itself represents a key factor that governs the locations of nucleosomes. Different DNA sequences exhibit different affinities for the histone proteins, and as such, they form nucleosomes with probabilities that can differ by several orders of magnitude (9, 10). The dependence of nucleosome locations on DNA sequence originates from subtle differences in the intrinsic shape and flexibility of a specific DNA sequence, which lead to favorable electrostatic interactions between the DNA backbone and residues on the histone surface (11). In fact, this pronounced dependence on DNA sequence has led several authors to propose that a genetic code exists (12, 13) where the positions of 50% of nucleosomes in vivo are dictated by DNA sequence alone. Such a view, however, is not without controversy (14, 15),...
The grafting-through copolymerization of two distinct macromonomers via ring-opening metathesis polymerization is typically used to form statistical or diblock bottlebrush polymers with large total backbone degrees of polymerization (N BB) relative to that of the side-chains (N SC). Here, we demonstrate that Grubbs-type chemistry in the opposite limit, namely N BB ≪ N SC, produces well-defined materials with excellent control over ensemble-averaged properties, including molar mass, dispersity, composition, and number of branch points. The dependence of self-assembly on these molecular design parameters was systematically probed using small-angle X-ray scattering and self-consistent field theoretic simulations. Our analysis supports the notion that two-component bottlebrush copolymers with small N BB behave like miktoarm star polymers. The star-to-bottlebrush transition is quantifiable for both statistical and diblock sequences by unique signatures in the experimental scaling of domain spacing and simulated distribution of backbone/side-chain density within lamellar unit cells. These findings represent a conceptual framework that simplifies the synthesis of miktoarm star polymers when dispersity in the number of arms and composition can be tolerated. The analytical approach introduced to distinguish chain conformations in complex macromolecules also complements previous methods, for example, form factor scattering and rheology.
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