Beyond stiffness: Multiscale viscoelastic features as biomechanical markers for assessing cell types and states.

Cell mechanics are pivotal in regulating cellular activities, diseases progression, and cancer development. However, the understanding of how cellular viscoelastic properties vary in physiological and pathological stimuli remains scarce. Here, we develop a hybrid self-similar hierarchical theory-microrheology approach to accurately and efficiently characterize cellular viscoelasticity. Focusing on two key cell types associated with livers fibrosis-the capillarized liver sinusoidal endothelial cells and activated hepatic stellate cells-we uncover a universal two-stage power-law rheology characterized by two distinct exponents, αshort and αlong. The mechanical profiles derived from both exponents exhibit significant potential for discriminating among diverse cells. This finding suggests a potential common dynamic creep characteristic across biological systems, extending our earlier observations in soft tissues. Using a tailored hierarchical model for cellular mechanical structures, we discern significant variations in the viscoelastic properties and their distribution profiles across different cell types and states from the cytoplasm (elastic stiffness E1 and viscosity η), to a single cytoskeleton fiber (elastic stiffness E2), and then to the cell level (transverse expansion stiffness E3). Importantly, we construct a logistic-regression-based machine-learning model using the dynamic parameters that outperforms conventional cell-stiffness-based classifiers in assessing cell states, achieving an area under the curve of 97% vs. 78%. Our findings not only advance a robust framework for monitoring intricate cell dynamics but also highlight the crucial role of cellular viscoelasticity in discerning cell states across a spectrum of liver diseases and prognosis, offering new avenues for developing diagnostic and therapeutic strategies based on cellular viscoelasticity.

Decorated bacteria-cellulose ultrasonic metasurface.

Cellulose, as a component of green plants, becomes attractive for fabricating biocompatible flexible functional devices but is plagued by hydrophilic properties, which make it easily break down in water by poor mechanical stability. Here we report a class of SiO2-nanoparticle-decorated bacteria-cellulose meta-skin with superior stability in water, excellent machining property, ultrathin thickness, and active bacteria-repairing capacity. We further develop functional ultrasonic metasurfaces based on meta-skin paper-cutting that can generate intricate patterns of ~10 µm precision. Benefited from the perfect ultrasound insulation of surface Cassie-Baxter states, we utilize meta-skin paper-cutting to design and fabricate ultrathin (~20 µm) and super-light (<20 mg) chip-scale devices, such as nonlocal holographic meta-lens and the 3D imaging meta-lens, realizing complicated acoustic holograms and high-resolution 3D ultrasound imaging in far fields. The decorated bacteria-cellulose ultrasonic metasurface opens the way for exploiting flexible and biologically degradable metamaterial devices with functionality customization and key applications in advanced biomedical engineering technologies.