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Flow-sensor

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made with VMD

The human body is protected by self-healing mechanisms, one of them being instant blood clotting at a bleeding site after blood vessel injury. What triggers the formation of a blood clot? Researchers found that a protein on blood platelets, called GPIbα, functions as a sensor of so-called high shear flow caused by bleeding. A loop-shaped, 17-amino-acid-long, segment of GPIb&alpha, the β-switch, acts as the flow sensor. Once a blood vessel is injured, bleeding increases shear stress due to blood flow at the wound, which in turn induces the β-switch to change from a loose, loop-shape to an elongated, hairpin-shape, the latter referred to by researchers as a β-hairpin. This conformational change makes GPIbα stick better to the damaged vessel and eventually leads to blood clotting, which heals the vessel. In a prior study (see the Jul 2008 highlight, Molecular Flow Sensor Triggers Wound Healing), Molecular dynamics simulations using NAMD and VMD provided already a microscopic view of the flow-induced loop to β-hairpin transition. A recent study extended the investigation of the remarkable biological flow sensor, detailing the flow rate needed to trigger it and identifying the detailed sensor mechanism. A combination of simulation and mathematical analysis revealed the β-switch as a system of two stable states, one disordered, with loop geometry and one ordered, with β-hairpin geometry. Normal flow prefers the disordered state; high shear flow prefers the ordered state, inducing thereby the life saving transition. More on our flow sensor website.