This is mainly due to the electrostatic interaction between the positively charged side chains of LY2109761 cost apomyoglobin and the negatively charged regions of heparin that leads to the formation of protein-GAG complexes. This interaction may partially mask the charge�Ccharge repulsion between the neighboring apomyoglobin molecules thereby determining a considerable increase in the local concentration of protein, which is a factor favoring rapid fibrillation . Our experimental observation that heparininduced acceleration of fibril formation is overturned when salts are added lends weight to this concept. Given the strong dependence of lag phase on heparin concentration , we postulate that heparin templates the monomers or oligomers to associate thereby reducing the lag phase of the W7FW14F apomyoglobin 129830-38-2 fibrillization process. This hypothesis is substantiated by the finding that at the highest heparin concentration used, the aggregation rate in the early stage of the process was four-times higher than that observed in the absence of heparin, and the fraction of soluble protein was strongly reduced . Taken together, these results suggest that heparin promotes the formation of a higher concentration of nuclei starting from monomeric soluble species and/or oligomeric aggregates. The FTIR spectra recorded soon after aggregation onset were consistent with rapid formation of cross-b rich nuclei acting as seeds for fibril formation. This conclusion corroborates the concept that heparin provides a spatially organized network that keeps protein molecules together thus allowing them to interact with each other . In this context, it is noteworthy that, at a low heparin concentration, 40 apomyoglobin molecules are bound to each heparin molecule . The large molar excess of protein over heparin could also be indicative of the binding of heparin to oligomeric, rather than to monomeric forms of apomyoglobin. At increasing heparin concentrations, the ratio of apomyoglobin to heparin decreases from 40 to 5, which is consistent with the possibility that heparin binds monomeric instead of oligomeric forms of apomyoglobin. However, we can not exclude that, at the highest concentration used, heparin might induce conformational changes leading to a more extended, ordered spatial orientation of protein molecules in the early formed aggregated complexes.