Single-cell mechanics provides a sensitive and quantitative means for probing amyloid-β peptide and neuronal cell interactions

Valentin Lulevich, Christopher C. Zimmer, Hyun Seok Hong, Lee-Way Jin, Gang-yu Liu

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

By using a highly sensitive technique of atomic force microscopy-based single-cell compression, the rigidity of cultured N2a and HT22 neuronal cells was measured as a function of amyloid-β42 (Aβ42) protein treatment. Aβ42 oligomers led to significant cellular stiffening; for example, 90-360% higher force was required to reach 80% deformation for N2a cells. Disaggregated or fibrillar forms of Aβ42 showed much less change. These observations were explained by a combination of two factors: (i) incorporation of oligomer into cellular membrane, which resulted in an increase in the Young's modulus of the membrane from 0.9 ± 0.4 to 1.85 ± 0.75 MPa for N2a cells and from 1.73 ± 0.90 to 5.5 ± 1.4 MPa for HT22 cells, and (ii) an increase in intracellular osmotic pressure (e.g., from 7 to 40 Pa for N2a cells) through unregulated ion influx. These findings and measurements provide a deeper, more characteristic, and quantitative insight into interactions between cells and Aβ42 oligomers, which have been considered the prime suspect for initiating neuronal dysfunction in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)13872-13877
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number31
DOIs
StatePublished - Aug 3 2010

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Keywords

  • Alzheimer's disease
  • Atomic force microscopy
  • Cell mechanics
  • Neuronal dysfunction
  • Young's moduli

ASJC Scopus subject areas

  • General

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