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The binding of plasma fibrinogen with both single-walled and multi-walled carbon nanotubes (SWNTs and MWNTs) has been examined. Specifically, our absorbance study indicated that MWNTs were coated with multi-layers of fibrinogen to render a “hard protein corona,” while SWNTs were adsorbed with thin layers of the protein to precipitate out of the aqueous phase. In addition, static quenching as a result of energy transfer from fluorescently labeled fibrinogen to their nanotube substrates was revealed by Stern-Volmer analysis. When exposed to HT-29 cells, the nanotubes and fibrinogen could readily dissociate, possibly stemming from their differential affinities for the amphiphilic membrane bilayer.