The mechanism by which ECM elasticity induces lineage specification of stem cells has not been clearly understood. Integrins are well-documented mechanosensors that are positioned at the beginning of the sensing pathway. By using an antibody specifically recognizing the active conformation of β1 integrin, we observed that β1 integrin activation in bone marrow mesenchymal stem cells (BMMSCs) was induced by soft substrate to a significantly greater degree than by stiff substrate. In contrast, however, the level of cell surface integrin on soft substrate was significantly lower than that on stiff substrate. Soft substrate markedly enhanced the internalization of integrin, and this internalization was mediated mainly through caveolae/raft-dependent endocytosis. The inhibition of integrin internalization blocked the neural lineage specification of BMMSCs on soft substrate. Furthermore, soft substrate also repressed the bone morphogenetic protein (BMP)/Smad pathway at least partially through integrin-regulated BMP receptor endocytosis. A theoretical analysis based on atomic force microscopy (AFM) data indicated that integrin-ligand complexes are more easily ruptured on soft substrate; this outcome may contribute to the enhancement of integrin internalization on soft substrate. Taken together, our results suggest that ECM elasticity affects integrin activity and trafficking to modulate integrin BMP receptor internalization, thus contributing to stem cell lineage specification.integrin trafficking | mesencymal stem cells | neurogenic lineage | traction force M echanical environment plays an important role in regulating cellular function and behavior, including proliferation, migration, apoptosis, and differentiation (1-3). It has been shown recently that the mechanical properties (e.g., elasticity) of adhesion substrates modulate stem cell fate in both 2D (4, 5) and 3D (6) cultures. However, the mechanism by which mechanical properties of ECM affect the chemical signaling processes has not been clearly understood.Mechanical stimuli induce changes in focal adhesion (FA) protein activities and FA remodeling (7,8). The growth and elongation of FAs vary with changes in substrate stiffness, indicating that ECM elasticity regulates FA assembly (4). FA complexes consist of many signaling molecules (including Src, Cas, vinculin, and integrins), which can undergo tension-dependent conformational changes to affect kinase activity, phosphorylation site availability, intracellular localization, and/or ligand affinity (9-12). Among these molecules, integrins are necessary for most mechanosensing processes and are positioned at the beginning of the sensing pathway (13).We aimed to explore the mechanism by which stem cells sense ECM elasticity, especially the role of β1 integrin in bone marrow mesenchymal stem cells (BMMSCs) (14). Activation of β1 integrin in BMMSCs was significantly greater on softer than on stiffer substrate. Most importantly, the intracellular localization of β1 integrin varied with substrate elasticity, being pres...

A simple and rapid photoelectrochemical (PEC) sensor was developed for the label-free detection of a phosphoprotein (α-casein) based on a zirconium based porphyrinic metal-organic framework (MOF), PCN-222, which exhibited an enhanced photocurrent response toward dopamine under the O-saturated aqueous media. In this work, in terms of PEC measurements and cyclic voltammetry, the PEC behaviors of PCN-222 in aqueous media were thoroughly investigated for the first time. Additionally, in the virtue of the steric hindrance effect from the coordination of the phosphate groups and inorganic Zr-O clusters as binding sites in PCN-222, this biosensor showed high sensitivity for detecting α-casein and the limit of detection (LOD) was estimated to be 0.13 μg mL. Moreover, the proposed method provides a promising platform for clinic diagnostic and therapeutics.

The Darboux transformations (DTs) associated with the well-known ZS-AKNS spectral problem are regarded as discrete spectral problems. Two kinds of integrable symplectic maps are derived from them through nonlinearization procedures. As an application, they are used to calculate the finite genus solutions of some new integrable lattice models constructed from these DTs.

A Zr-based metal-organic framework with zinc tetrakis(carboxyphenyl)-porphyrin (ZnTCPP) groups (MOF-525-Zn) was utilized to develop a novel electrochemiluminescence (ECL) biosensor for highly sensitive protein kinase activity assay. In this work, in terms of ECL measurements and cyclic voltammetry, the cathodic ECL behaviors of MOF-525-Zn in aqueous media were thoroughly investigated for the first time. The photoelectric active groups ZnTCPP on the MOF-525-Zn frameworks could promote the generation of singlet oxygen ((1)O2) via a series of electrochemical and chemical reactions, resulting in a strong and stable red irradiation at 634 nm. Additionally, the surfactant tetraoctylammonium bromide (TOAB) further facilitated dissolved oxygen to interact with the active sites ZnTCPP of MOF-525-Zn. Furthermore, the inorganic Zr-O clusters of MOF-525-Zn were simultaneously served as the recognition sites of phosphate groups. And then, an ultrasensitive ECL sensor was proposed for protein kinase A (PKA) activity detection with a linear range from 0.01 to 20 U mL(-1) and a sensitive detection limit of 0.005 U mL(-1). This biosensor can also be applied for quantitative kinase inhibitor screening. Finally, it exhibits good performance with high stability and acceptable fabrication reproducibility, which provide a valuable strategy for clinic diagnostics and therapeutics.

Two integrable symplectic maps are constructed through nonlinearization of the discrete linear spectral problems in the Lax pair of the Hirota equation, i.e. the lattice sine-Gordon equation. As an application, these maps are used to calculate the finite genus solutions of the Hirota equation and the closely related lattice potential MKdV equation, i.e. the special H3 model in the Adler–Bobenko–Suris list.