Probing Charge Transfer of Aβ-Proteins Examined Using Two-Dimensional Materials as Raman Spectroscopic Platform

When and Where

Nov 30, 2022
2:15pm - 2:30pm

Sheraton, 2nd Floor, Back Bay B

Presenter

Wujoon Cha

Chaejeong Heo

Sang Hyub Lee

Seok Jun Yun

Byeong Wook Cho

Taewoo Ha

Young Hee Lee

Co-Author(s)

Wujoon Cha^1,2,Chaejeong Heo^1,2,Sang Hyub Lee^1,2,Seok Jun Yun³,Byeong Wook Cho^1,2,Taewoo Ha^1,2,Young Hee Lee^1,2

Institute for Basic Science¹,Sungkyunkwan University²,Oak Ridge National Laboratory³

Abstract

Wujoon Cha^1,2,Chaejeong Heo^1,2,Sang Hyub Lee^1,2,Seok Jun Yun³,Byeong Wook Cho^1,2,Taewoo Ha^1,2,Young Hee Lee^1,2

Institute for Basic Science¹,Sungkyunkwan University²,Oak Ridge National Laboratory³

We report distinguished charge transfer of amyloid-β (Aβ) proteins at different aggregation stages with two-dimensional (2D) materials that can potentially be critical for understanding the fibrillization mechanism and developing an early-stage diagnostic method of Alzheimer’s disease. We previously identified notable variations in conductance of Aβ proteins in monomer, oligomer, and fibril forms measured by THz spectroscopy, suggesting significant changes in electronic structures as Aβ fibrillizes [1]. In this work, we show that Aβs exhibit distinct charge-transfer behavior depending on their aggregated states when interacting with monolayer graphene and molybdenum disulfide (MoS2). In particular, we found that small and soluble Aβ monomers p-doped both graphene and MoS2 sheets while large and insoluble Aβ fibrils n-doped them. These findings provide critical insights into the electronic properties of Aβs that could be essential to identifying the onset of neurotoxic Aβ fibril formation and developing a rapid, label-free diagnosis based on two-dimensional materials. In Alzheimer’s disease (AD), the accumulation of senile plaques, dominantly composed of fibrillized Aβs in the cerebral cortex, has been identified as the primary indication of degeneracy. Therefore, early diagnosis of AD is strongly dependent on the ability to detect the emergence of toxic Aβ oligomers and fibrils. It has been suggested that charge transfer plays a key role in the formation and the interaction of proteins [2]. Although Aβ states can be identified based on ‘fingerprints’ of vibrational modes observed with optical spectroscopies, there is a gap in knowledge about the electronic properties of Aβ that varies significantly as Aβ fibrillizes. To address this gap, we used Raman spectroscopy to probe Aβ proteins interacting with two-dimensional materials that are sensitive to molecular charge transfer. Graphene, an atomically thin semimetal, and monolayer MoS2, a semiconductor with a direct bandgap, react sensitively to charge-transfer-induced doping. The shifts in the carrier concentrations and in the Fermi levels can be distinguished from the characteristic Raman bands in graphene (G and 2D) and in MoS2 (E2g and A1g) [3,4]. Here, we conducted Raman spectroscopy on monolayer graphene and MoS2 added with Aβ proteins at different fibrillization stages - monomer, oligomer, and fibril. The graphene and MoS2 sheets were prepared via chemical vapor deposition and transferred on a Si/SiO2 300-nm substrate separately. Then,10 µM protein solutions were loaded and dried in air for subsequent Raman spectroscopy. A statistically significant (p-value < 0.0001) distinction was shown for doping due to monomers and fibrils. Taking the effects of buffer media into account, we observed that, in both graphene and MoS2, monomer withdrew electrons and p-doped while fibril injected electrons and n-doped on average. This was evidenced by the upshift(downshift) of G and 2D band, sharpening(broadening) of G band, and decrease(increase) of 2D to G intensity ratio for graphene with monomer(fibril). Similarly, in MoS2, A1g frequency increased(decreased) and width stiffened(softened) by monomer(fibril). The changes in carrier concentrations were calculated based on the relative positions of the signature Raman bands. In turn, we estimated that the monomers and fibrils shifted the graphene Fermi level by approximately -1.0 eV and +1.9 eV, respectively. The contrary charge-transfer behavior suggests that the electronic states of Aβ, such as its highest occupied (HOMO) and lowest unoccupied (LUMO) molecular orbital levels, shift significantly as Aβ fibrillizes. The transition point from p-doping to n-doping can serve as a marker for the onset of toxic Aβ aggregates. [1] Heo et al., ACS Nano, 14, 6548 (2020). [2] Cordes et al., Chem. Soc. Rev., 38, 892 (2009). [3] Das et al., Nat. Nanotech., 3, 210 (2008). [4] Zhong et al., Chem. Soc. Rev., 44, 2757 (2015).