Gradient Mechanical Properties Facilitate <i>Arabidopsis</i> Trichome as Mechanosensor

It has been reported that <i>Arabidopsis thaliana</i> leaf trichome can act as a mechanosensory switch, transducing mechanical stimuli into physiological signals, mainly through a buckling instability to focus external force (e.g., exerted by insects) on the base of trichome. The material and structural properties of trichomes remain largely unknown in this buckling instability. In this report, we mainly focused on material standpoint to explore the possible mechanism facilitating the buckling instability. We observed that the Young’s modulus of trichome cell wall decreased gradually from branch to the base region of trichome. Interestingly, we also found a corresponding decline of calcium concentration on the trichome cell wall. Results of finite element method (FEM) simulation suggested that such a gradient distribution of Young’s modulus significantly promotes force focusing and buckling instability on the base of trichome. It is indicated that <i>Arabidopsis</i> trichome has developed into an active mechanosensor benefiting from gradient cell wall mechanical properties

Patterning Cellular Alignment through Stretching Hydrogels with Programmable Strain Gradients

The graded mechanical properties (e.g., stiffness and stress/strain) of excellular matrix play an important role in guiding cellular alignment, as vital in tissue <i>reconstruction with proper functions</i>. Though various methods have been developed to engineer a graded mechanical environment to study its effect on cellular behaviors, most of them failed to distinguish stiffness effect from stress/strain effect during mechanical loading. Here, we construct a mechanical environment with programmable strain gradients by using a hydrogel of a linear elastic property. When seeding cells on such hydrogels, we demonstrate that the pattern of cellular alignment can be rather precisely tailored by substrate strains. The experiment is in consistency with a theoritical prediction when assuming that focal adhesions (FAs) would drive a cell to reorient to the directions where they are most stable. A fundamental theory has also been developed and is excellent in agreement with the complete temporal alignment of cells. This work not only provides important insights into the cellular response to the local mechanical microenvironment but can also be utilized to engineer patterned cellular alignment that can be critical in tissue remodeling and regenerative medicine applications

Fabrication of Microscale Hydrogels with Tailored Microstructures based on Liquid Bridge Phenomenon

Microscale hydrogels (microgels) find widespread applications in various fields, such as drug delivery, tissue engineering, and biosensing. The shape of the microgels is a critical parameter that can significantly influence their function in these applications. Although various methods have been developed (e.g., micromolding, photolithography, microfluidics, and mechanical deformation method), it is still technically challenging to fabricate microgels with tailored microstructures. In this study, we have developed a simple and versatile method for preparing microgels by stretching hydrogel precursor droplets between two substrates to form a liquid bridge. Microgels with tailored microstructures (e.g., barrel-like, dumbbell-like, or funnel-like shapes) have been achieved through adjusting the distance between and the hydrophobicity of the two substrates. The developed method holds great potential to impact multiple fields, such as drug delivery, tissue engineering, and biosensing

Melting Away Pain: Decay of Thermal Nociceptor Transduction during Heat-Induced Irreversible Desensitization of Ion Channels

Thermal transient receptor potential channels play a key role in thermal sensation. Although predictive models exist for temperature-dependent transduction through these channels and for the associated sensations of pain, the ability to predict irreversible desensitization has been lacking. We explored the role of irreversible ion channel desensitization in pain sensation and hypothesized that desensitization of ion channels would follow the kinetics similar to the denaturation of catalytic enzymes. We therefore proposed a three-state model to simulate the kinetic of temperature-sensitive ion channels from the closed state through opening and irreversible thermal desensitization. We tested the model against data obtained in vivo from a feline model. The theoretical model predicts all experimental data with reasonable accuracy, and represents an important step toward the ability for understanding of the molecular basis of nociceptor signaling providing the possibility to design local anesthesia regimens and to the prediction of postoperative pain

Facial Layer-by-Layer Engineering of Upconversion Nanoparticles for Gene Delivery: Near-Infrared-Initiated Fluorescence Resonance Energy Transfer Tracking and Overcoming Drug Resistance in Ovarian Cancer

Development of multidrug resistance (MDR) contributes to the majority of treatment failures in clinical chemotherapy. We report facial layer-by-layer engineered upconversion nanoparticles (UCNPs) for near-infrared (NIR)-initiated tracking and delivery of small interfering RNA (siRNA) to enhance chemotherapy efficacy by silencing the MDR1 gene and resensitizing resistant ovarian cancer cells to drug. Layer-by-layer engineered UCNPs were loaded with MDR1 gene-silencing siRNA (MDR1-siRNA) by electrostatic interaction. The delivery vehicle enhances MDR1-siRNA cellular uptake, protects MDR1-siRNA from nuclease degradation, and promotes endosomal escape for silencing the MDR gene. The intrinsic photon upconversion of UCNPs provides an unprecedented opportunity for monitoring intracellular attachment and release of MDR1-siRNA by NIR-initiated fluorescence resonance energy transfer occurs between donor UCNPs and acceptor fluorescence dye-labeled MDR1-siRNA. Enhanced chemotherapeutic efficacy in vitro was demonstrated by cell viability assay. The developed delivery vehicle holds great potential in delivery and imaging-guided tracking of therapeutic gene targets for effective treatment of drug-resistant cancers