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The binding of fibrinogen to various nanoparticles can result in protein unfolding and exposure of cryptic epitopes that subsequently interact with cell surface receptors. This response is dependent on the size, charge, and concentration of the nanoparticle. Here we examine the binding kinetics of human fibrinogen to negatively charged poly(acrylic acid)-coated gold nanoparticles ranging in size from 7 to 22 nm. These particles have previously been shown to elicit an inflammatory response in human cells. The larger nanoparticles bound fibrinogen with increasing affinity and a slower dissociation rate. Each fibrinogen molecule could accommodate two 7 nm nanoparticles but only one when the diameter increased to 10 nm. Nanoparticles larger than 12 nm bound multiple fibrinogen molecules in a positively cooperative manner. However, in the presence of excess nanoparticle, fibrinogen induced aggregation of the …