Nuclear mechanical properties are inherently scale-dependent, arising from a hierarchical architecture that spans DNA, chromatin, the nuclear envelope, and condensates. Experimental techniques and theoretical models are integrated into a cohesive multiscale framework linking nanoscale structural features to organelle-level mechanical behavior. These insights open new directions in mechanodiagnostics, mechanotherapy, and nucleus-targeting nanomedicine. ABSTRACT The cell nucleus serves as the central hub of genetic information and a dynamic, multiscale mechanosensor that regulates critical cellular behaviors, such as gene expression and cell migration. Functioning as a complex soft matter system, the nucleus comprises a hierarchical architecture spanning from nanoscale DNA and nucleosomes to microscale chromosome territories and the nuclear envelope. This multiscale structural organization endows the nucleus with scale-dependent mechanical properties—such as stiffness and viscoelasticity—that are fundamental to cellular mechanotransduction and the strict regulation of nuclear entry for therapeutic nanoparticles. This review emphasizes the recent advances in understanding the multiscale architecture and mechanics of the cell nucleus. We compare experimental technologies for probing nuclear mechanics, alongside emerging multiscale theoretical models that transform these qualitative observations into quantitative, predictive frameworks for mechanobiology and nanomedicine. Finally, we highlight the translational implications of nuclear mechanics on nuclear-targeted nanomedicine, mechanodiagnosis, and mechanotherapy.

YouTube video by Emma Forever Yoga

La Candelaria University Hospital in Tenerife has started producing custom mechanotherapy tools using a 3D printer, with positive results.

La Candelaria University Hospital in Tenerife has started producing custom mechanotherapy tools using a 3D printer, with positive results.

Read the full paper: An atom-edged magnetic nanomotor for cancer mechanotherapy

Fibrotic scarring persistently challenges urethral reconstruction. This study introduces a conformal, wearable ultrasound bioelectronic system that overcomes this by reprogramming fibroblast fate. The device activates a developmental Wnt–FGF10 axis, driving fibroblasts toward a regenerative FGF10 + phenotype that promotes angiogenesis and matrix remodeling while suppressing collagen deposition, thereby redirecting healing away from fibrosis and toward functional tissue regeneration. ABSTRACT Postoperative fibrotic complications persistently challenge urethral reconstruction due to dysregulated stromal repair and poor graft integration. Conventional rigid ultrasound transducers lack anatomical conformity on dynamic tissues, limiting therapeutic efficacy. Here, we introduce a conformal, wearable low-intensity pulsed ultrasound (LIPUS) bioelectronic system that overcomes these constraints via controlled adhesion printing and liquid metal interconnects. This low-cost (<$20), flexible device ensures stable acoustic coupling and programmable mechanostimulation while maintaining mechanical integrity and biocompatibility under repeated use. In a rabbit model of full-thickness urethral defect, LIPUS significantly improves luminal patency and urinary flow function, promotes angiogenesis and elastic fiber regeneration, while suppressing collagen deposition and pro-inflammatory macrophage infiltration. Integrated multi-omics and single-nucleus RNA sequencing reveal that LIPUS activates the Wnt pathway to drive fibroblast differentiation into a terminally differentiated FGF10 + subset (FB3), which engages in regenerative crosstalk with mural cells via FGF10-FGFR2b signaling and calcium dynamics. Wnt inhibition abrogates this process, confirming mechanistic specificity. This study bridges flexible bioelectronics with deep mechanobiology, providing new insights into how mechanical stimulation can redirect fibroblast fate and override pathological fibrosis, offering a scalable therapeutic framework for fibrotic disorders.