Surfactant Properties and Interface Induced Aggregation of Tau Proteins

Abstract

Abnormal aggregation of microtubule associating protein, tau, into neurofibrillar aggregates, due to protein mutations, is a defining hallmark of several neurological diseases. Recent research indicates that the polymerization of soluble tau proteins into paired helical filaments may be influenced by the hydrophobic properties of its monomers, the presence of inducers and the local environment. In this work, we will discuss our results from using five HTau 40 protein variations: wild type (WT), pseudophosphorylated (7-phos), mutations on the binding domain (P301L), assembly incompetent protein (I277/308P), and mutations on the N terminal (R5L), to study template induced adsorption and aggregation of Tau proteins at a model hydrophobic interface.Traditional biophysical techniques such as surface pressure vs. time (adsorption isotherms) are used to record adsorption kinetics. We find that even though tau is a soluble protein, it is highly surface active at nanomolar concentrations and demonstrate a two-step adsorption to the hydrophobic interface. Further, the adsorption kinetics is dependent both on the concentration and protein mutation. However, almost all the proteins studied here demonstrate a saturation concentration of a few hundred nanomoles, which is much lower than the bulk concentration where protein aggregation is recorded. Using an active microrheology technique unique to our lab, we also find that surface viscosity of the adsorbed protein films increase by orders of magnitude with time, indicating protein-protein interactions. However, the kinetics of this increase depends on the mutations on the protein. Further, TEM images of the protein solution obtained from the surface indicate the formation of protein oligomers. In summary, our results indicate that the soluble Tau proteins have interesting surfactant properties even at nanomolar concentrations that may play a role in their aggregation during Alzheimer's disease.