Single-cell mechanics provides a sensitive and quantitative means for probing amyloid-beta peptide and neuronal cell interactions.
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-beta42 (Abeta42) protein treatment. Abeta42 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 Abeta42 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 Abeta42 oligomers, which have been considered the prime suspect for initiating neuronal dysfunction in Alzheimer's disease.
Lulevich
Valentin
V
Department of Chemistry, University of California, Davis, CA 95616, USA.
Zimmer
Christopher C
CC
Hong
Hyun-seok
HS
Jin
Lee-way
LW
Liu
Gang-yu
GY
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D051379:Mice; D009474:Neurons / Q000737:chemistry* / Q000502:physiology; D017711:Nonlinear Dynamics; D055503:Protein Multimerization
D016229:Amyloid beta-Peptides