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https://www.selleckchem.com/products/bx-795.html Macrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine the role of the mechanically activated cation channel Piezo1 in macrophage polarization and sensing of microenvironmental stiffness. We show that macrophages lacking Piezo1 exhibit reduced inflammation and enhanced wound healing responses. Additionally, macrophages expressing the transgenic Ca2+ reporter, Salsa6f, reveal that Ca2+ influx is dependent on Piezo1, modulated by soluble signals, and enhanced on stiff substrates. Furthermore, stiffness-dependent changes in macrophage function, both in vitro and in response to subcutaneous implantation of biomaterials in vivo, require Piezo1. Finally, we show that positive feedback between Piezo1 and actin drives macrophage activation. Together, our studies reveal that Piezo1 is a mechanosensor of stiffness in macrophages, and that its activity modulates polarization responses.Update rules, which describe how individuals adjust their behavior over time, affect the outcome of social interactions. Theoretical studies have shown that evolutionary outcomes are sensitive to model details when update rules are imitation-based but are robust when update rules are self-evaluation based. However, studies of self-evaluation based rules have focused on homogeneous population structures where each individual has the same number of neighbors. Here, we consider heterogeneous population structures represented by weighted networks. Under weak selection, we analytically derive the condition for strategy success, which coincides with the classical condition of risk-dominance. This condition holds for all weighted networks and distributions of aspiration levels, and for individualized ways of self-evaluation. Our findings recover previous results as specia

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