We report a solid-state, nanofiber-based optical sensor for detecting proteins with an anionic fluorescent dendrimer (AFD). The AFD was encapsulated in cellulose acetate (CA) electrospun nanofibers, which were deacetylated to cellulose to generate secondary porous structures that are desirable for enhancing molecular interactions, and thus better signaling. The protein sensing properties of the fibers were characterized by monitoring the fluorescence response of cytochrome c (cyt c), hemoglobin (Hgb), and bovine serum albumin (BSA) as a function of concentration. Effective quenching was observed for the metalloproteins, cyt c and Hgb. The effect was primarily due to energy transfer of the imbedded fluorescent dendrimers to the protein, as both proteins contain heme portions. Electron transfer, caused through the electrostatic effects in the binding of the anionic dendrimer to the positive patches of globular proteins, could be responsible as well. BSA, on the other hand, triggered a "turn-on" response in fluorescence, suggesting the negatively charged BSA reduces the pi-pi stacking of the partially dispersed, negatively charged dendritic fluorophores through repulsion forces, which results in an increase in fluorescence. Stern-Volmer constants (K(sv)) of the electrospun fibers were found to be 3.4 x 10(5) and 1.7 x 10(6) M(-1) for cyt c and Hgb, respectively. The reusability of the nanofibers is excellent: the nanofibers demonstrated less than 15% change of fluorescence intensity signal in a 5-cycle test.