Neurite initiation is the first step in neuronal development and occurs spontaneously in soft tissue environments. Although the mechanisms regulating the morphology of migratory cells on rigid substrates in cell culture are widely known, how soft environments modulate neurite initiation remains elusive. Using hydrogel cultures, pharmacologic inhibition, and genetic approaches, we reveal that paxillin-linked endocytosis and adhesion are components of a bistable switch controlling neurite initiation in a substrate modulus-dependent manner. On soft substrates, most paxillin binds to endocytic factors and facilitates vesicle invagination, elevating neuritogenic Rac1 activity and expression of genes encoding the endocytic machinery. By contrast, on rigid substrates, cells develop extensive adhesions, increase RhoA activity and sequester paxillin from the endocytic machinery, thereby delaying neurite initiation. Our results highlight paxillin as a core molecule in substrate modulus-controlled morphogenesis and define a mechanism whereby neuronal cells respond to environments exhibiting varying mechanical properties.
We have developed an optical method for real-time monitoring of cellular motion in a natural environment with nanometer resolution. From the motion driven by small optical forces, we measured dynamic viscoelastic responses of living cells in the linear reversible region. Cytoplasmic gel-to-sol transition that was due to the disruption of the actin-filament framework was detected, and a linear release of Ca(2+) from intracellular storage that was related to submicrometer cell deformation was observed. The method was shown to be a powerful tool for studying the natural response of cells to mechanical perturbation.
Previous studies have found that the non-invasive blood pressure measurement method based on the oscillometric method is inaccurate when an arrhythmia occurs. Therefore, we propose a high-sensitivity pulse sensor that can measure the hemodynamic characteristics of the pulse wave and then estimate the blood pressure. When an arrhythmia occurs, the hemodynamics of the pulse wave are abnormal and change the morphology of the pulse wave. Our proposed sensor can measure the occurrence of ectopic beats from the radial artery, and the detection algorithm can reduce the error of blood pressure estimation caused by the distortion of ectopic beats that occurs when the pulse wave is measured. In this study, we tested patients with premature atrial contraction (PAC) or premature ventricular contraction (PVC) and analyzed the morphology of the pulse waves when the sensor detected the ectopic beats. We discuss the advantages of using the Moens–Korteweg equation to estimate the blood pressure of patients with arrhythmia, which is different from the oscillometric method. Our research provides a possible arrhythmia detection method for wearable devices and can accurately estimate blood pressure in a non-invasive way during an arrhythmia.
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