Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

MEMBRANE PROTEIN ENGINEERING FOR SENSING TRANSIENT MOLECULAR HALLMARKS IN NEURODEGENERATION Devika Vikraman; Liviu Movileanu ; Syracuse University, Department of Physics, Syracuse , NY, USA The seminal discovery of a GGGGCC hexanucleotide repeat expansion in the open reading frame 72 on chromosome 9, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD; C9-ALS/FTD), is a significant advance in neurodegeneration research. Over the past decade, it has been frequently proposed that one mechanism of neuronal damage is the aberrant accumulation of unnatural dipeptide repeat (DPR) proteins in patients' brains in the early stages of the disease. Aggregation of arginine-rich DPR (RDPR) proteins is considered the most toxic. A persistent limitation in further therapeutic development and understanding of ALS/FTD pathologies is the lack of high-resolution technologies for detecting early RDPR cluster formation. In this talk, I will discuss our recent progress in developing a protein nanopore sensing platform for single-molecule detection of RDPR aggregates at their earliest stages, before phase-separating conditions. We recently engineered a single polypeptide chain nanopore that accommodates many negative charges within its lumen. In this way, RDPR monomers and small oligomers can be readily detected through a high-affinity, nonspecific binding mechanism for these intrinsically disordered proteins, which are hallmarks of ALS and FTD. This sensing platform shows promise for further studies to uniquely profile the kinetics and dynamics of RDPR oligomer formation in these pathologies.

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