Journal article
Electric Double Layer Phenomena Near Surfaces Irreversibly Trigger Assembly of Tau Protein
Journal of the American Chemical Society, v 148(14), pp 15035-15047
15 Apr 2026
PMID: 41921971
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The reversible folding and assembly of the human brain protein tau are regulated by charge neutralization through limited and reversible phosphorylation, enabling tau to bind tubulin and maintain the structural integrity of neuronal microtubules. However, in neurodegenerative diseases like Alzheimer's and related tauopathies, tau becomes hyperphosphorylated, detaches from tubulin, and irreversibly assembles into β-structured amyloid filaments responsible for neuronal death. In previous work, we showed that charge neutralization via Faradaic electroreduction of cationic residues in tau and other intrinsically disordered proteins can mimic phosphorylation to trigger protein condensation, folding, and assembly. Here, we demonstrate that even non-Faradaic effects─including large electric fields and concentration gradients in the electric double layer, together with spatial ordering of ions at the solution-electrode interface─can induce folding and assembly of tau, its microtubule-binding region K18, and a 19-residue tau peptide (jR2R3 P301L) containing a mutation known to induce early aggregation
and
. Assembly occurs on different electrode materials at identical effective electric fields, demonstrating independence from the electrode hydrophobicity and electronic structure. Surface-enhanced infrared absorption and plasmon resonance spectroscopies show that near-surface electric fields of ∼1 MV/cm trigger K18 folding and assembly. Ion ordering and charge screening near electrodes at higher salt concentrations (50 vs 1 mM) also reduce Coulombic repulsion between protein monomers and their cationic residues, promoting folding and assembly. Overall, these results show that interfacial electric fields and other non-Faradaic processes can reveal and drive protein misfolding and aggregation, hallmarks of tauopathies and prion-related neurodegenerative diseases.
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Details
- Title
- Electric Double Layer Phenomena Near Surfaces Irreversibly Trigger Assembly of Tau Protein
- Creators
- Eloise Masquelier - University of California SystemMadeline Hicks - California Institute of TechnologyNicholas Watkins - University of California SystemNorleakvisoth Lim - University of California SystemJustin Yi - University of California SystemDaniel E Morse - University of California SystemLior Sepunaru - University of California SystemMichael J Gordon - University of California System
- Publication Details
- Journal of the American Chemical Society, v 148(14), pp 15035-15047
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Nanomaterials Institute
- Web of Science ID
- WOS:001731646200001
- Scopus ID
- 2-s2.0-105035883563
- Other Identifier
- 991022207177404721
UN Sustainable Development Goals (SDGs)
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary