Vibrational circular dichroism shows unusual sensitivity to protein fibril formation and development in solution

Similar, unusually large vibrational circular dichroism (VCD) spectra in the amide I and II region for aqueous solutions of the proteins lysozyme and insulin are presented under conditions of heating at low pH that are known to induce fibril formation. Centrifugation allows separation of a fibril gel phase from a proto-filament supernatant phase where VCD indicative of the presence of proto-filaments, compared to the VCD of native protein, is observed. Development of even larger VCD over longer time periods, growing in magnitude and changing in relative intensities, is followed with in situ solution-state VCD measurements of a single sample of insulin. These spectra demonstrate that VCD possesses unusual sensitivity to fibril growth and development in solution. Correlation of these VCD spectra to AFM or SEM images of corresponding fibril samples will be carried out in the future.