Integrins are a family of transmembrane glycoprotein signaling receptors that can transmit bioinformation bidirectionally across the plasma membrane. Integrin αIIbβ3 is expressed at a high level in platelets and their progenitors, where it plays a central role in platelet functions, hemostasis, and arterial thrombosis. Integrin αIIbβ3 also participates in cancer progression, such as tumor cell proliferation and metastasis. In resting platelets, integrin αIIbβ3 adopts an inactive conformation. Upon agonist stimulation, the transduction of inside-out signals leads integrin αIIbβ3 to switch from a low-to high-affinity state for fibrinogen and other ligands. Ligand binding causes integrin clustering and subsequently promotes outside-in signaling, which initiates and amplifies a range of cellular events to drive essential platelet functions such as spreading, aggregation, clot retraction, and thrombus consolidation. Regulation of the bidirectional signaling of integrin αIIbβ3 requires the involvement of numerous interacting proteins, which associate with the cytoplasmic tails of αIIbβ3 in particular. Integrin αIIbβ3 and its signaling pathways are considered promising targets for antithrombotic therapy. This review describes the bidirectional signal transduction of integrin αIIbβ3 in platelets, as well as the proteins responsible for its regulation and therapeutic agents that target integrin αIIbβ3 and its signaling pathways.
Natural articular cartilage has ultralow friction even at high squeezing pressure. Biomimicking cartilage with soft materials has been and remains a grand challenge in the fields of materials science and engineering. Inspired by the unique structural features of the articular cartilage, as well as by its remarkable lubrication mechanisms dictated by the properties of the superficial layers, a novel archetype of cartilage-mimicking bilayer material by robustly entangling thick hydrophilic polyelectrolyte brushes into the subsurface of a stiff hydrogel substrate is developed. The topmost soft polymer layer provides effective aqueous lubrication, whereas the stiffer hydrogel layer used as a substrate delivers the load-bearing capacity. Their synergy is capable of attaining low friction coefficients (order 0.010) under heavily loaded conditions (order 10 MPa contact pressure) in water environment, a performance incredibly close to that of natural articular cartilage. The bioinspired material can maintain low friction even when subjected to 50k reciprocating cycles under high contact pressure, with almost no wear observed on the sliding track. These findings are theoretically explained and compounded by multiscale simulations used to shed light on the mechanisms responsible for this remarkable performance. This work opens innovative technology routes for developing cartilage-mimicking ultralow friction soft materials.
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