Compaction and clustering of a heterogeneous polymer by biomolecular crowding.

Inspired by bacterial chromosome organization, we study the compaction and clustering of a heterogeneous ring polymer in a crowded medium using molecular dynamics simulations. The polymer consists of several large monomers interspersed along the backbone and small intervening monomers. In a crowded medium, the entropy of crowding particles or crowders favors the collapse of chain molecules, such as chromosomes.

Anomalous Water Penetration in Al Dissolution.

The physicochemical characterization of trivalent ions is limited due to a lack of accurate force fields. By leveraging the latest machine learning force field to model aqueous AlCl, we discover that upon dissolution of Al, water molecules beyond the second hydration shell are involved in the hydration process. A combination of scissoring of coordinating water is followed by synchronized secondary motion of water in the second solvation shell due to hydrogen bonding.

Hi-C-guided many-polymer model to decipher 3D genome organization.

We propose a high-throughput chromosome conformation capture data-based many-polymer model that allows us to generate an ensemble of multi-scale genome structures. We demonstrate the efficacy of our model by validating the generated structures against experimental measurements and employ them to address key questions regarding genome organization. Our model first confirms a significant correlation between chromosome size and nuclear positioning.

Kinetic Model for the Desensitization of G Protein-Coupled Receptor.

Desensitization of G-protein-coupled receptors (GPCR) is a general regulatory mechanism adopted by biological organisms against overstimulation of G protein signaling. Although the details of the mechanism are extensively studied, it is not easy to gain an overarching understanding of the process constituted by a multitude of molecular events with vastly differing time scales. To offer a semiquantitative yet predictive understanding of the mechanism, we formulate a kinetic model for the G protein signaling and desensitization by considering essential biochemical steps from ligand binding to receptor internalization.

Water Hydrogen-Bond Mediated Layer by Layer Alignment of Lipid Rafts as a Precursor of Intermembrane Processes.

Lipid rafts, which are dynamic nanodomains in the plasma membrane, play a crucial role in intermembrane processes by clustering together and growing in size within the plane of the membrane while also aligning with each other across different membranes. However, the physical origin of layer by layer alignment of lipid rafts remains to be elucidated. Here, by using fluorescence imaging and synchrotron X-ray reflectivity in a phase-separated multilayer system, we find that the alignment of raft-mimicking L domains is regulated by the distance between bilayers.

Glycolytic oscillations under periodic drivings.

In many living organisms displaying circadian rhythms, the intake of energy often occurs in a periodic manner. Glycolysis is a prototypical biochemical reaction that exhibits a self-sustained oscillation under continuous injection of glucose. Here we study the effect of periodic injection of glucose on the glycolytic oscillation from a dynamical systems perspective.

TMAO Destabilizes RNA Secondary Structure via Direct Hydrogen Bond Interactions.

Trimethylamine -oxide (TMAO) is an osmolyte that accumulates in cells in response to osmotic stress. TMAO stabilizes proteins by the entropic stabilization mechanism, which pictures TMAO as a nanocrowder that predominantly destabilizes the unfolded state. However, the mechanism of action of TMAO on RNA is much less understood.

Moderate activity of RNA chaperone maximizes the yield of self-spliced pre-RNA in vivo.

CYT-19 is a DEAD-box protein whose adenosine-triphosphate (ATP)-dependent helicase activity facilitates the folding of group I introns in precursor RNA (pre-RNA) of (). In the process, they consume a substantial amount of ATP. While much of the mechanistic insight into CYT-19 activity has been gained through the studies on the folding of group I intron ribozyme, the more biologically relevant issue, namely the effect of CYT-19 on the self-splicing of pre-RNA, remains largely unexplored.

Solvent Quality Dependent Osmotic Pressure of Polymer Solutions in Two Dimensions.

Confined in two-dimensional planes, polymer chains comprising dense monolayer solutions are segregated from each other because of topological interaction. Although the segregation is inherent in two dimensions (2D), the solution may display different properties depending on the solvent quality. Among others, it is well-known in both theory and experiment that the osmotic pressure (Π) in the semidilute regime displays solvent quality dependent increases with the area fraction (ϕ) (or monomer concentration, ρ), that is, Π ∼ ϕ for good solvents and Π ∼ ϕ for Θ solvents.

Polymer Physics-Based Classification of Neurons.

Recognizing that diverse morphologies of neurons are reminiscent of structures of branched polymers, we put forward a principled and systematic way of classifying neurons that employs the ideas of polymer physics. In particular, we use 3D coordinates of individual neurons, which are accessible in recent neuron reconstruction datasets from electron microscope images. We numerically calculate the form factor, F(q), a Fourier transform of the distance distribution of particles comprising an object of interest, which is routinely measured in scattering experiments to quantitatively characterize the structure of materials.

Olfactory responses of are encoded in the organization of projection neurons.

The projection neurons (PNs), reconstructed from electron microscope (EM) images of the olfactory system, offer a detailed view of neuronal anatomy, providing glimpses into information flow in the brain. About 150 uPNs constituting 58 glomeruli in the antennal lobe (AL) are bundled together in the axonal extension, routing the olfactory signal received at AL to mushroom body (MB) calyx and lateral horn (LH). Here we quantify the neuronal organization in terms of the inter-PN distances and examine its relationship with the odor types sensed by .

Dissecting the cosegregation probability from genome architecture mapping.

Genome architecture mapping (GAM) is a recently developed methodology that offers the cosegregation probability of two genomic segments from an ensemble of thinly sliced nuclear profiles, enabling us to probe and decipher three-dimensional chromatin organization. The cosegregation probability from GAM binned at 1 Mb, which thus probes the length scale associated with the genomic separation greater than 1 Mb, is, however, not identical to the contact probability obtained from Hi-C, and its correlation with interlocus distance measured with fluorescence in situ hybridization is not so good as the contact probability. In this study, by using a polymer-based model of chromatins, we derive a theoretical expression of the cosegregation probability as well as that of the contact probability and carry out quantitative analyses of how they differ from each other.

Location of the TEMPO moiety of TEMPO-PC in phosphatidylcholine bilayers is membrane phase dependent.

The (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) moiety tethered to the headgroup of phosphatidylcholine (PC) lipid is employed in spin labeling electron paramagnetic resonance spectroscopy to probe the water dynamics near lipid bilayer interfaces. Due to its amphiphilic character, however, TEMPO spin label could partition between aqueous and lipid phases, and may even be stabilized in the lipid phase. Accurate assessment of the TEMPO-PC configuration in bilayer membranes is essential for correctly interpreting the data from measurements.

Origin of loose bound of the thermodynamic uncertainty relation in a dissipative two-level quantum system.

Thermodynamic uncertainty relations (TURs), originally discovered for classical systems, dictate the tradeoff between dissipation and fluctuations of irreversible current, specifying a minimal bound that constrains the two quantities. In a series of efforts to extend the relation to the one under more generalized conditions, it has been noticed that the bound is less tight in open quantum processes. To study the origin of the loose bounds, we consider an external field-driven transition dynamics of a two-level quantum system weakly coupled to the bosonic bath as a model of an open quantum system.

Extracting multi-way chromatin contacts from Hi-C data.

There is a growing realization that multi-way chromatin contacts formed in chromosome structures are fundamental units of gene regulation. However, due to the paucity and complexity of such contacts, it is challenging to detect and identify them using experiments. Based on an assumption that chromosome structures can be mapped onto a network of Gaussian polymer, here we derive analytic expressions for n-body contact probabilities (n > 2) among chromatin loci based on pairwise genomic contact frequencies available in Hi-C, and show that multi-way contact probability maps can in principle be extracted from Hi-C.

Cost-precision trade-off relation determines the optimal morphogen gradient for accurate biological pattern formation.

Spatial boundaries formed during animal development originate from the pre-patterning of tissues by signaling molecules, called morphogens. The accuracy of boundary location is limited by the fluctuations of morphogen concentration that thresholds the expression level of target gene. Producing more morphogen molecules, which gives rise to smaller relative fluctuations, would better serve to shape more precise target boundaries; however, it incurs more thermodynamic cost.

Polymer brush-induced depletion interactions and clustering of membrane proteins.

We investigate the effect of mobile polymer brushes on proteins embedded in biological membranes by employing both Asakura-Oosawa type of theoretical model and coarse-grained molecular dynamics simulations. The brush polymer-induced depletion attraction between proteins changes non-monotonically with the size of brush. The depletion interaction, which is determined by the ratio of the protein size to the grafting distance between brush polymers, increases linearly with the brush size as long as the polymer brush height is shorter than the protein size.

Extreme parsimony in ATP consumption by 20S complexes in the global disassembly of single SNARE complexes.

Fueled by ATP hydrolysis in N-ethylmaleimide sensitive factor (NSF), the 20S complex disassembles rigid SNARE (soluble NSF attachment protein receptor) complexes in single unraveling step. This global disassembly distinguishes NSF from other molecular motors that make incremental and processive motions, but the molecular underpinnings of its remarkable energy efficiency remain largely unknown. Using multiple single-molecule methods, we found remarkable cooperativity in mechanical connection between NSF and the SNARE complex, which prevents dysfunctional 20S complexes that consume ATP without productive disassembly.

Thermodynamic Optimality of Glycolytic Oscillations.

Temporal order in living matters reflects the self-organizing nature of dynamical processes driven out of thermodynamic equilibrium. Because of functional reasons, the period of a biochemical oscillation must be tuned to a specific value with precision; however, according to the thermodynamic uncertainty relation (TUR), the precision of the oscillatory period is constrained by the thermodynamic cost of generating it. After reviewing the basics of chemical oscillations using the Brusselator as a model system, we study the glycolytic oscillation generated by octameric phosphofructokinase (PFK), which is known to display a period of several minutes.

Thermodynamic uncertainty relation to assess biological processes.

We review the trade-offs between speed, fluctuations, and thermodynamic cost involved with biological processes in nonequilibrium states and discuss how optimal these processes are in light of the universal bound set by the thermodynamic uncertainty relation (TUR). The values of the uncertainty product Q of TUR, which can be used as a measure of the precision of enzymatic processes realized for a given thermodynamic cost, are suboptimal when the substrate concentration is at the Michaelis constant, and some of the key biological processes are found to work around this condition. We illustrate the utility of Q in assessing how close the molecular motors and biomass producing machineries are to the TUR bound, and for the cases of biomass production (or biological copying processes), we discuss how their optimality quantified in terms of Q is balanced with the error rate in the information transfer process.

A unified framework for inferring the multi-scale organization of chromatin domains from Hi-C.

Chromosomes are giant chain molecules organized into an ensemble of three-dimensional structures characterized with its genomic state and the corresponding biological functions. Despite the strong cell-to-cell heterogeneity, the cell-type specific pattern demonstrated in high-throughput chromosome conformation capture (Hi-C) data hints at a valuable link between structure and function, which makes inference of chromatin domains (CDs) from the pattern of Hi-C a central problem in genome research. Here we present a unified method for analyzing Hi-C data to determine spatial organization of CDs over multiple genomic scales.

Revisiting the organization of Polycomb-repressed domains: 3D chromatin models from Hi-C compared with super-resolution imaging.

The accessibility of target gene, a factor critical for gene regulation, is controlled by epigenetic fine-tuning of chromatin organization. While there are multiple experimental techniques to study change of chromatin architecture with its epigenetic state, measurements from them are not always complementary. A qualitative discrepancy is noted between recent super-resolution imaging studies, particularly on Polycomb-group protein repressed domains in Drosophila cell.