Raman and SERS Spectra of Human Myelin Basic Protein in Cerebrospinal Fluid

Raman spectroscopy (RS) provides detailed information on molecular structure but remains challenging for low-scattering proteins in complex media. Myelin basic protein (MBP) is a key structural component of central nervous system myelin and a clinically relevant molecule in demyelinating disorders; however, to the best of our knowledge, its Raman signature in solution has not been reported. In this work, Raman and surface-enhanced Raman spectroscopy (SERS) were employed to characterize purified human myelin basic protein (MBP) in aqueous solution and cerebrospinal fluid (CSF). Quasi-spherical silver nanoparticles were used as SERS elements, yielding enhancement factors of 10⁵ and increasing sensitivity to MBP-associated spectral changes at low concentrations. The MBP spectrum exhibited vibrational modes primarily associated with amide II and amide III bands, as well as aromatic side-chain contributions. Comparative analysis of MBP, CSF, and MBP-spiked CSF samples revealed significant spectral overlap, limiting discrimination based solely on peak positions. To overcome this limitation, spectral correlation and band-intensity-ratio analyses were applied, revealing reproducible trends associated with increasing MBP content. While individual MBP bands are not exclusive, the observed spectral patterns demonstrate the sensitivity of RS and SERS to MBP-induced spectral changes in CSF. These findings should be interpreted as a proof-of-concept in a single-donor CSF matrix.