cooperativity , a universal property of biological macromolecules , is typically characterized by a hill slope , which can provide fundamental information about binding sites and interactions . 
 we demonstrate , via simulations and single molecule fret experiments , that molecular heterogeneity lowers bulk cooperativity from the intrinsic value for the individual molecules . as heterogeneity 
 is common in smfret experiments , appreciation of its influence on fundamental measures of cooperativity is critical for deriving accurate molecular models .