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Hair, or hair-like fibrillar structures, are ubiquitous in biology, from fur on the bodies of mammals, over trichomes of plants, to the mastigonemes on the flagella of single-celled organisms. While these long and slender protuberances are passive, they are multifunctional and help to mediate interactions with the environment. They provide thermal insulation, sensory information, reversible adhesion, and surface modulation (e.g., superhydrophobicity). This review will present various functions that biological hairs have been discovered to carry out, with the hairs spanning across six orders of magnitude in size, from the millimeter-thick fur of mammals down to the nanometer-thick fibrillar ultrastructures on bateriophages. The hairs are categorized according to their functions, including protection (e.g., thermal regulation and defense), locomotion, feeding, and sensing. By understanding the versatile functions of biological hairs, bio-inspired solutions may be developed across length scales.

The fibrous extracellular matrix (ECM) is vital for tissue regeneration and impacts implanted device treatments. Previous research on fibrous biomaterials shows varying cellular reactions to surface orientation, often due to unclear interactions between surface topography and substrate elasticity. Our study addresses this gap by achieving the rapid creation of hydrogels with diverse fibrous topographies and varying substrate moduli through a surface printing strategy. Cells exhibit heightened traction force on nanopatterned soft hydrogels, particularly with randomly distributed patterns compared with regular soft hydrogels. Meanwhile, on stiff hydrogels featuring an aligned topography, optimal cellular mechanosensing is observed compared to random topography. Mechanistic investigations highlight that cellular force-sensing and adhesion are influenced by the interplay of pattern deformability and focal adhesion orientation, subsequently mediating stem cell differentiation. Our findings highlight the importance of combining substrate modulus and topography to guide cellular behavior in designing advanced tissue engineering biomaterials.

Mechanical forces play a crucial role in cellular processes, including ferroptosis, a form of regulated cell death associated with various diseases. However, the mechanical aspects of organelle lipid droplets (LDs) during ferroptosis are poorly understood. In this study, we designed and synthesized a fluorescent probe, TPE-V1, to enable real-time monitoring of LDs\' viscosity using a dual-channel fluorescence-on model (red channel at 617 nm and NIR channel at 710 nm). The fluorescent imaging of using TPE-V1 was achieved due to the integrated mechanisms of the twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE). Through dual-emission channel fluorescence imaging, we observed the enhanced mechanical energy of LDs triggering cellular mechanosensing, including ferroptosis and cell deformation. Theoretical calculations confirmed the probe\'s behavior, showing that high-viscosity media prevented the rotation processes and restored fluorescence quenching in low viscosity. These findings suggest that our TICT-TPE design strategy provides a practical approach to study LDs\' mechanical properties during ferroptosis. This development enhances our understanding of the interplay between mechanical forces and LDs, contributing to the knowledge of ferroptotic cell death and potential therapeutic interventions targeting dysregulated cell death processes.

The extracellular matrix (ECM) plays a crucial role in regulating cellular behaviors and functions. However, the impact of ECM topography on muscle cell adhesion and differentiation remains poorly understood from a mechanosensing perspective. In this study, we fabricated aligned and random electrospun polycaprolactone (PCL) nanofibers to mimic the structural characteristics of ECM. Mechanism investigations revealed that the orientation of nanofibers promoted C2C12 polarization and myogenesis through Rac-related signaling pathways. Conversely, cells cultured on random fibers exhibited spreading behavior mediated by RhoA/ROCK pathways, resulting in enhanced stress fiber formation but reduced capacity for myogenic differentiation. Our findings highlight the critical role of an ECM structure in muscle regeneration and damage repair, providing novel insights into mechanosensing mechanisms underlying muscle injury diseases.

Stem cells are regulated not only by biochemical signals but also by biophysical properties of extracellular matrix (ECM). The ECM is constantly monitored and remodeled because the fate of stem cells can be misdirected when the mechanical interaction between cells and ECM is imbalanced. A well-defined ECM model for bone marrow-derived human mesenchymal stem cells (hMSCs) based on supramolecular hydrogels containing reversible host-guest crosslinks is fabricated. The stiffness (Young\'s modulus E) of the hydrogels can be switched reversibly by altering the concentration of non-cytotoxic, free guest molecules dissolved in the culture medium. Fine-adjustment of substrate stiffness enables the authors to determine the critical stiffness level E* at which hMSCs turn the mechano-sensory machinery on or off. Next, the substrate stiffness across E* is switched and the dynamic adaptation characteristics such as morphology, traction force, and YAP/TAZ signaling of hMSCs are monitored. These data demonstrate the instantaneous switching of traction force, which is followed by YAP/TAZ signaling and morphological adaptation. Periodical switching of the substrate stiffness across E* proves that frequent applications of mechanical stimuli drastically suppress hMSC proliferation. Mechanical stimulation across E* level using dynamic hydrogels is a promising strategy for the on-demand control of hMSC transcription and proliferation.

Polysaccharides κ-carrageenan (κ-Car) have become a predominant source in developing bioactive materials. We aimed to develop biopolymer composite materials of κ-Car with coriander essential oil (CEO) (κ-Car-CEO) films for fibroblast-associated wound healing. Initially, we loaded the CEO in to κ-Car and CEO through homogenization and ultrasonication to fabricate composite film bioactive materials. After performing morphological and chemical characterizations, we validated the developed material functionalities in both in vitro and in vivo models. The chemical and morphological analysis with physical structure, swelling ratio, encapsulation efficiency, CEO release, and water barrier properties of films examined and showed the structural interaction of κ-Car and CEO-loaded into the polymer network. Furthermore, the bioactive applications of CEO release showed initial burst release followed by controlled release from the κ-Car composite film with fibroblast (L929) cell adhesive capabilities and mechanosensing. Our results proved that the CEO-loaded into the κ-Car film impacts cell adhesion, F-actin organization, and collagen synthesis, followed by in vitro mechanosensing activation, further promoting wound healing in vivo. Our innovative perspectives of active polysaccharide (κ-Car)-based CEO functional film materials could potentially accomplish regenerative medicine.

Many marine invertebrates have planktonic larval and benthic juvenile/adult stages. When the planktonic larvae are fully developed, they must find a favorable site to settle and metamorphose into benthic juveniles. This transition from a planktonic to a benthic mode of life is a complex behavioral process involving substrate searching and exploration. Although the mechanosensitive receptor in the tactile sensor has been implicated in sensing and responding to surfaces of the substrates, few have been unambiguously identified. Recently, we identified that the mechanosensitive transient receptor potential melastatin-subfamily member 7 (TRPM7) channel, highly expressed in the larval foot of the mussel Mytilospsis sallei, was involved in substrate exploration for settlement. Here, we show that the TRPM7-mediated Ca2+ signal was involved in triggering the larval settlement of M. sallei through the calmodulin-dependent protein kinase kinase β/AMP-activated protein kinase/silk gland factor 1 (CaMKKβ-AMPK-SGF1) pathway. It was found that M. sallei larvae preferred the stiff surfaces for settlement, on which TRPM7, CaMKKβ, AMPK, and SGF1 were highly expressed. These findings will help us to better understand the molecular mechanisms of larval settlement in marine invertebrates, and will provide insights into the potential targets for developing environmentally friendly antifouling coatings for fouling organisms.

Microgravity exposure during spaceflight causes the disordered regulation of liver function, presenting a specialized mechano-biological coupling process. While YAP/TAZ serves as a typical mechanosensitive pathway involved in hepatocyte metabolism, it remains unclear whether and how it is correlated with microgravity-induced liver dysfunction. Here, we discussed liver function alterations induced by spaceflight or simulated effects of microgravity on Earth. The roles of YAP/TAZ serving as a potential bridge in connecting liver metabolism with microgravity were specifically summarized. Existing evidence indicated that YAP/TAZ target gene expressions were affected by mechanotransductive pathways and phase separation, reasonably speculating that microgravity might regulate YAP/TAZ activation by disrupting these pathways via cytoskeletal remodeling or nuclear deformation, or disturbing condensates formation via diffusion limit, and then breaking liver homeostasis.

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