Background-Laminins are major components of basement membranes, well located to interact with platelets upon vascular injury. Laminin-111 (α 1 β 1 γ 1 ) is known to support platelet adhesion but is absent from most blood vessels, which contain isoforms with the α 2 , α 4 , or α 5 chain. Whether vascular laminins support platelet adhesion and activation and the significance of these interactions in hemostasis and thrombosis remain unknown. Methods and Results-Using an in vitro flow assay, we show that laminin-411 (α 4 β 1 γ 1 ), laminin-511 (α 5 β 1 γ 1 ), and laminin-521 (α 5 β 2 γ 1 ), but not laminin-211 (α 2 β 1 γ 1 ), allow efficient platelet adhesion and activation across a wide range of arterial wall shear rates. Adhesion was critically dependent on integrin α 6 β 1 and the glycoprotein Ib-IX complex, which binds to plasmatic von Willebrand factor adsorbed on laminins. Glycoprotein VI did not participate in the adhesive process but mediated platelet activation induced by α 5 -containing laminins. To address the significance of platelet/laminin interactions in vivo, we developed a platelet-specific knockout of integrin α 6 . Platelets from these mice failed to adhere to laminin-411, laminin-511, and laminin-521 but responded normally to a series of agonists. α 6 β 1 -Deficient mice presented a marked decrease in arterial thrombosis in 3 models of injury of the carotid, aorta, and mesenteric arterioles. The tail bleeding time and blood loss remained unaltered, indicating normal hemostasis. Conclusions-This study reveals an unsuspected important contribution of laminins to thrombus formation in vivo andsuggests that targeting their main receptor, integrin α 6 β 1 , could represent an alternative antithrombotic strategy with a potentially low bleeding risk. (Circulation. 2013;128:541-552.)Key Words: blood platelets ◼ integrin α 6 β 1 ◼ laminin ◼ thrombosis
Solid walls become increasingly important when miniaturizing fluidic circuitry to the micron scale or smaller. 1 They limit achievable flow-rates due to friction and high pressure drop, and are plagued by fouling 2 . Approaches to reduce the wall interactions have been explored using hydrophobic coatings 3,4 , liquid-infused porous surfaces [4][5][6] , nanoparticle surfactant jamming 7 , changing the surface electronic structure 8 , electrowetting 9,10 , surface tension pinning 11,12 , and atomically flat channels 13 . An interesting idea is to avoid the solid walls altogether. Droplet microfluidics achieves this, but requires continuous flow of both the liquid transported inside the droplets and the outer carrier liquid 14 . We demonstrate a new approach, where wall-less aqueous liquid channels are stabilised by a quadrupolar magnetic field that acts on a surrounding immiscible magnetic liquid. This creates self-healing, uncloggable, and near-frictionless liquidin-liquid microfluidic channels that can be deformed and even closed in real time without ever touching a solid wall. Basic fluidic operations including valving, mixing, and 'magnetostaltic' pumping can be achieved by moving permanent magnets having no physical contact with the channel. This wall-less approach is compatible with conventional microfluidics, while opening unique prospects for implementing nanofluidics without excessively high pressures.Magnetic forces have been used to avoid contact with the walls of a device by levitation of particles or live cells in suspension 15 , and a first attempt to make wall-less microfluidic channels resulted in continuous 'magnetic antitubes' of water surrounded by an aqueous paramagnetic salt solution 16 using
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