Programmable and Reversible Integrin-Mediated Cell Adhesion Reveals Hysteresis in Actin Kinetics that Alters Subsequent Mechanotransduction.

Dynamically evolving adhesions between cells and extracellular matrix (ECM) transmit time-varying signals that control cytoskeletal dynamics and cell fate. Dynamic cell adhesion and ECM stiffness regulate cellular mechanosensing cooperatively, but it has not previously been possible to characterize their individual effects because of challenges with controlling these factors independently. Therefore, a DNA-driven molecular system is developed wherein the integrin-binding ligand RGD can be reversibly presented and removed to achieve cyclic cell attachment/detachment on substrates of defined stiffness. Using this culture system, it is discovered that cyclic adhesion accelerates F-actin kinetics and nuclear mechanosensing in human mesenchymal stem cells (hMSCs), with the result that hysteresis can completely change how hMSCs transduce ECM stiffness. Results are dramatically different from well-known results for mechanotransduction on static substrates, but are consistent with a mathematical model of F-actin fragments retaining structure following loss of integrin ligation and participating in subsequent repolymerization. These findings suggest that cyclic integrin-mediated adhesion alters the mechanosensing of ECM stiffness by hMSCs through transient, hysteretic memory that is stored in F-actin.

T Cell engineering for cancer immunotherapy by manipulating mechanosensitive force-bearing receptors.

T cell immune responses are critical for in both physiological and pathological processes. While biochemical cues are important, mechanical cues arising from the microenvironment have also been found to act a significant role in regulating various T cell immune responses, including activation, cytokine production, metabolism, proliferation, and migration. The immune synapse contains force-sensitive receptors that convert these mechanical cues into biochemical signals. This phenomenon is accepted in the emerging research field of immunomechanobiology. In this review, we provide insights into immunomechanobiology, with a specific focus on how mechanosensitive receptors are bound and triggered, and ultimately resulting T cell immune responses.

Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation.

During mesenchymal development, the sources of mechanical forces transduced by cells transition over time from predominantly cell-cell interactions to predominantly cell-extracellular matrix (ECM) interactions. Transduction of the associated mechanical signals is critical for development, but how these signals converge to regulate human mesenchymal stem cells (hMSCs) mechanosensing is not fully understood, in part because time-evolving mechanical signals cannot readily be presented in vitro. Here, we established a DNA-driven cell culture platform that could be programmed to present the RGD peptide from fibronectin, mimicking cell-ECM interactions, and the HAVDI peptide from N-cadherin, mimicking cell-cell interactions, through DNA hybridization and toehold-mediated strand displacement reactions. The platform could be programmed to mimic the evolving cell-ECM and cell-cell interactions during mesenchymal development. We applied this platform to reveal that RGD/integrin ligation promoted cofilin phosphorylation, while HAVDI/N-cadherin ligation inhibited cofilin phosphorylation. Cofilin phosphorylation upregulated perinuclear apical actin fibers, which deformed the nucleus and thereby induced YAP nuclear localization in hMSCs, resulting in subsequent osteogenic differentiation. Our programmable culture platform is broadly applicable to the study of dynamic, integrated mechanobiological signals in development, healing, and tissue engineering.

Cathode/gel polymer electrolyte integration design based on continuous composition and preparation technique for high performance lithium ion batteries.

Gel polymer electrolytes (GPEs) combine the high ionic conductivity of liquid electrolytes and good safety assurance of solid electrolytes. However, the poor interfacial contact between electrode materials and electrolyte is still a big obstacle to the high performance of solid-state batteries. Herein, an integrated cathode/GPE based on continuous composition and preparation technic is obtained by simple UV curing. The improved interfacial contact between cathode and GPE helps to facilitate the fast ions transfer at the interface. Compared with cells assembled with separated cathode and GPE, the cells with integrated cathode-GPE showed much lower interfacial impedance, lower potential polarization and more stable cycling property. This work provided a low-cost natural material gelatin and a simple UV irradiation method to prepare an integrated cathode and gel polymer electrolyte for solid-state lithium batteries. The capacity retention of the cells assembled from integrated structure was 91.4% which was much higher than that of the non-integrated cells (80.9%) after 200 cycles.

A flexible Cellulose/Methylcellulose gel polymer electrolyte endowing superior Li+ conducting property for lithium ion battery.

With the advent of gel polymer electrolyte (GPE), a series of safety problems of lithium ion batteries have been resolved. However, poor self-standing property, the low ionic conductivity and Li+ transference number are still the obstacles that impede the practical application of GPE. Herein, a flexible and eco-friendly GPE is designed using allyl-modified cellulose with methylcellulose through simple UV curing. The crosslinked structure facilitates the integrity of GPE during use, and methylcellulose guarantees the high affinity to liquid electrolyte and improve interfacial compatibility. The specific polar functional groups (OH, OCH3 and COC) in GPE cooperate to enhance the lithium salt dissociation, anion immobilization and lithium ion transporting and enable the high Li+ transference number (0.902) and ion conductivity (4.36 × 10-3 S cm-1). The assembled Li/GPE/LiFePO4 coin cells possess high initial discharge capacity of 150.6 mA h g-1 and a high capacity retention of 91.6 % after 100 cycles.

An environment-friendly crosslinked binder endowing LiFePO4 electrode with structural integrity and long cycle life performance.

Lithium iron phosphate (LiFePO4) is one of the most widely used cathode materials of lithium ion batteries. However, its commercial binder polyvinylidene fluoride (PVDF) is costly, less environmental-friendly and unstable during the long cycling process because of the weak van der Waals forces between the PVDF binder and electrode materials. Herein, an aqueous binder was designed using methacrylate-modified gelatin through UV photo-crosslinking. The crosslinked network and specific functional groups (carboxyl and amino) of the gelatin binder are superior in stabilizing the LiFePO4 electrode structure during long cycles by mitigating the formation of cracks and suppressing the detachment of electrode materials from the Al current collector. The LiFePO4 electrode with gelatin binder displays a high capacity of 140.3 mA h g-1 with 90.1% retention after 300 cycles at 0.5C, which are both superior to that of the PVDF binder (only 114.4 mA h g-1 and 74.8%). This work provides a promising binder to replace the commercial PVDF binder for practical application in energy storage systems.