Nature Materials最新文献

Metastases arise from a multistep process during which tumour cells face several microenvironmental mechanical challenges, which influence metastatic success. However, how circulating tumour cells (CTCs) adapt their mechanics to such microenvironments is not fully understood. Here we report that the deformability of CTCs affects their haematogenous dissemination and identify mechanical phenotypes that favour metastatic extravasation. Combining intravital microscopy with CTC-mimicking elastic beads, mechanical tuning in tumour lines and profiling of tumour-patient-derived cells, we demonstrate that the inherent mechanical properties of circulating objects dictate their ability to enter constraining vessels. We identify cellular viscosity as a rheostat of CTC circulation and arrest, and show that cellular viscosity is crucial for efficient extravasation. Moreover, we find that mechanical properties that favour extravasation and subsequent metastatic outgrowth can be opposite. Altogether, our results establish CTC viscosity as a key biomechanical parameter that shapes several steps of metastasis.

Biological processes are regulated by chemical and mechanical signals, yet how these signalling modalities interact remains poorly understood. Here we identify a crosstalk between tissue stiffness and long-range chemical signalling in the developing Xenopus laevis brain. Targeted knockdown of the mechanosensitive ion channel Piezo1 in retinal ganglion cells or in the brain tissue surrounding retinal ganglion cells causes pathfinding errors in vivo. In the brain parenchyma, Piezo1 downregulation decreases the expression of the diffusive long-range chemical guidance cues Semaphorin3A (Sema3A) and Slit1, which instruct turning responses in distant cells. Furthermore, Piezo1 knockdown results in tissue softening due to reduced expression of the adhesion proteins NCAM1 and N-cadherin. Targeted depletion of NCAM1 and N-cadherin similarly reduces tissue stiffness and Sema3A expression. Conversely, increasing environmental stiffness ex vivo enhances tissue-level force generation and Slit1 and Sema3A expression. Finally, in vivo stiffening of soft brain regions induces ectopic Sema3A production via a Piezo1-dependent mechanism. Overall, these findings demonstrate that tissue mechanics locally modulates the availability of diffusive, long-range chemical signals, thus influencing cell function at sites distant from the mechanical cue.

Lithium dendrite intrusion in solid-state batteries limits fast charging and causes short-circuiting, yet the underlying regulating mechanisms are not well-understood. Here we discover that heterogeneous Ag⁺ doping dramatically affects lithium intrusion into Li_6.6La₃Zr_1.6Ta_0.4O₁₂ (LLZO), a brittle solid electrolyte. Nanoscale Ag⁺ doping is achieved by thermally annealing a 3-nm-thick metallic coating on LLZO, inducing Ag-Li ion exchange and Ag diffusion into grains and grain boundaries. Density functional theory calculations and experimental characterization show negligible impact on the electronic properties and surface wettability from Ag⁺ incorporation. Mechanically, nanoindentation experiments show a fivefold increase in the mechanical force required to fracture the surface Ag⁺-doped LLZO, indicating substantial doping-induced surface toughening. Operando microprobe scanning electron microscopy experiments show that the Ag⁺-doped LLZO surface exhibits improved lithium plating at >250 mA cm^-2 and an electroplating diameter that is expanded by over fourfold, even under an extreme indentation stress of 3 GPa. This demonstrates enhanced defect tolerance in LLZO, rather than electronic or adhesion effects. Our study reveals a chemo-mechanical mechanism via surface heterogeneous doping, complementing present bulk design rules to minimize mechanical failures in solid-state batteries.