RESUMO
Mechanical force controls fundamental cellular processes in health and disease, and increasing evidence shows that the nucleus both experiences and senses applied forces. Such forces can lead to the nuclear translocation of proteins, but whether force controls nucleocytoplasmic transport, and how, remains unknown. Here we show that nuclear forces differentially control passive and facilitated nucleocytoplasmic transport, setting the rules for the mechanosensitivity of shuttling proteins. We demonstrate that nuclear force increases permeability across nuclear pore complexes, with a dependence on molecular weight that is stronger for passive than for facilitated diffusion. Owing to this differential effect, force leads to the translocation of cargoes into or out of the nucleus within a given range of molecular weight and affinity for nuclear transport receptors. Further, we show that the mechanosensitivity of several transcriptional regulators can be both explained by this mechanism and engineered exogenously by introducing appropriate nuclear localization signals. Our work unveils a mechanism of mechanically induced signalling, probably operating in parallel with others, with potential applicability across signalling pathways.
Assuntos
Núcleo Celular , Poro Nuclear , Transporte Ativo do Núcleo Celular/fisiologia , Núcleo Celular/metabolismo , Poro Nuclear/genética , Poro Nuclear/metabolismo , Transporte Proteico , Receptores Citoplasmáticos e Nucleares/metabolismoRESUMO
Fiber reinforcement is a crucial attribute of soft-bodied muscular hydrostats that have the ability to undergo large deformations and maintain their posture. Helically wound fibers around the cylindrical worm body help control the tube diameter and length. Geometric considerations show that a fiber winding angle of 54.7°, called the magic angle, results in a maximum enclosed volume. Few studies have combined both experimental and theoretical techniques to explore the effects of fiber winding at varied angles on the large deformation mechanics of fiber-reinforced elastomers (FRE). We fabricated FRE materials in transversely isotropic layouts varying from 0° to 90° using a custom filament winding technique and characterized the nonlinear stress-strain relationships using uniaxial and equibiaxial experiments. We used these data within a continuum mechanical framework to propose a novel constitutive model for incompressible FRE materials with embedded extensible fibers. The model includes individual contributions from the matrix and fibers in addition to coupled terms in strain invariants, I1 and I4. The deviatoric stress components show inversion at fiber orientation angles near the magic angle in the FRE composites. These results are useful in soft robotic applications and in the biomechanics of fiber-reinforced tissues such as the myocardium, arteries, and skin.
Assuntos
Artérias , Elastômeros , Anisotropia , Fenômenos Biomecânicos , Estresse MecânicoRESUMO
Wood boring is a feature of several insect species and is a major cause of severe and irreparable damage to trees. Adult females typically deposit their eggs on the stem surface under bark scales. The emerging hatchlings live within wood during their larval phase, avoiding possible predation, whilst continually boring and tunneling through wood until pupation. A study of wood boring by insects offers unique insights into the bioengineering principles that drive evolutionary adaptations. We show that larval mandibles of the coffee wood stem borer beetle (Xylotrechus quadripes: Cerambycidae) have a highly sharp cusp edge to initiate fractures in Arabica wood and a suitable shape to generate small wood chips that are suitable for digestion. Cuticle hardness at the tip is significantly enhanced through zinc-enrichment. A hollow architecture significantly reduces bending stresses at the mandibular base without compromising the structural integrity. Finite element model of the mandible showed highest stresses in the tip region; these decreased to significantly lower values at the start of the hollow section. A scaling model based on a fracture mechanics framework shows the importance of the mandible shape in generating optimal chip sizes. These findings contain general principles in tool design and put in focus interactions of insects and their woody hosts.