Comparative vibrational spectroscopy of intracellular tau and extracellular collagen I reveals parallels of gelation and fibrillar structure.

The N-terminal tau 2-19 peptide undergoes gelation, syneresis, and aggregation over a period of years. These changes may be approximated on a shorter time scale by agitation and partial dehydration. The anomalously enhanced (229 nm) ultraviolet resonance Raman (UVRR) imide II band reveals a common structural feature for gels of nondehydrated tau 2-19 and collagen I and insoluble paired helical filaments (PHFs) and collagen I of weak hydrogen bonding at proline carbonyls. Anomalous UVRR enhancement of amide bands at 229 nm results from gel structure, as demonstrated by increased amide absorption at the red edge for tau 2-19 gel and implies the involvement of water in gel structure. In aged, dehydrated tau 2-19 gel, proline carbonyls lose their bonds to water and tyrosine becomes deprotonated, as demonstrated by UVRR spectroscopy. The Fourier transform infrared (FTIR) amide I band shows that antiparallel beta-sheet structure increases with syneresis in the tau 2-19 hydrogel. The comparison of FTIR results for PHFs with collagen I gel and polyproline demonstrates that the secondary structure of PHFs is polyproline II. One implication of this assignment is that the fibrillation of hydrophilic tau is thermodynamically driven by the entropy gained as hydrogen-bonded water is freed, as for collagen I. The FTIR results also show that peptide domains culled from a longer protein do not necessarily fold into identical secondary structures. A pathological, sequential mechanism of gelation, syneresis, and fibrillation for tau in AD is suggested and is supported by the observation of amorphous neurofibrillary tangle development and fibrillation in vivo.