Steric repulsion introduced by loop constraints modulates the microphase separation of chromatins.

Within the confines of a densely populated cell nucleus, chromatin undergoes intricate folding, forming loops, domains, and compartments under the governance of topological constraints and phase separation. This coordinated process inevitably introduces interference between different folding strategies. In this study, we model interphase chromatins as block copolymers with hetero-hierarchical loops within a confined system. Employing dissipative particle dynamics simulations and scaling analysis, we aim to explain how the structure and distribution of loop domains modulate the microphase separation of chromatins. Our results highlight the correlation between the microphase separation of the copolymer and the length, heterogeneity, and hierarchically nested levels of the loop domains. This correlation arises from steric repulsion intrinsic to loop domains. The steric repulsion induces variations in chain stiffness (including local orientation correlations and the persistence length), thereby influencing the degree of phase separation. Through simulations of block copolymers with distinct groups of hetero-hierarchical loop anchors, we successfully reproduce changes in phase separation across diverse cell lines, under fixed interaction parameters. These findings, in qualitative alignment with Hi-C data, suggest that the variations of loop constraints alone possess the capacity to regulate higher-order structures and the gene expressions of interphase chromatins.

The effects of ageing on the biomechanical properties of root dentine and fracture.

OBJECTIVES: Knowledge of the mechanical behaviour of root dentine can facilitate better understanding of spontaneous vertical root fracture (VRF), an age-related disease initiated mainly at the root apex. We tested the hypothesis that the biomechanical properties of root dentine change with ageing. METHODS: Sixteen human premolars were divided into "old" (17-30 years) and "young" (50-80 years) groups. The elastic modulus, nano-hardness, micro-hardness, elemental contents, tubular density/area of root dentine in cervical, middle and apical root regions were evaluated using atomic force microscopy-based nano-indentation, Knoop indentation, scanning electron microscopy and energy dispersive X-ray spectroscopy, respectively. RESULTS: The apical dentine showed a lower nano-hardness, a lower elastic modulus, a lower calcium content, a lower calcium-to-phosphorus ratio and a smaller tubular density/area than the cervical dentine in both age groups, whereas spatial differences in micro-hardness were observed only in old roots. Compared with young dentine, old dentine showed a greater hardness, a higher elastic modulus, a greater mineral content and a smaller tubular size in the cervical portion, whereas the age-induced changes in tubular density were insignificant. Finite element analysis revealed that due to its higher elastic modulus, old apical dentine has a higher stress level than young dentine. CONCLUSIONS: The intrinsic material properties of root dentine have spatial variations, and they are altered by ageing. The higher stress level in old apical dentine may be one reason, if not the most important one, why spontaneous VRFs are more likely to occur in the elderly population.

Spatial distribution of the human enamel fracture toughness with aging.

A better understanding of the fracture toughness (KIC) of human enamel and the changes induced by aging is important for the clinical treatment of teeth cracks and fractures. We conducted microindentation tests and chemical content measurements on molar teeth from "young" (18 ≤ age ≤ 25) and "old" (55 ≤ age) patients. The KIC and the mineral contents (calcium and phosphorus) in the outer, the middle, and the inner enamel layers within the cuspal and the intercuspal regions of the crown were measured through the Vickers toughness test and Energy Dispersive X-Ray Spectroscopy (EDS), respectively. The elastic modulus used for the KIC calculation was measured through atomic force microscope (AFM)-based nanoindentation tests. In the outer enamel layer, two direction-specific values of the KIC were calculated separately (direction I, crack running parallel to the occlusal surface; direction II, perpendicular to direction I). The mean KIC of the outer enamel layer was lower than that of the internal layers (p<0.05). No other region-related differences in the mechanical properties were found in both groups. In the outer enamel layer, old enamel has a lower KIC, II and higher mineral contents than young enamel (p<0.05). The enamel surface becomes more prone to cracks with aging partly due to the reduction in the interprismatic organic matrix observed with the maturation of enamel.