title: Single-cell mechanics provides a sensitive and quantitative means for probing amyloid-beta peptide and neuronal cell interactions.
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-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.
authors.affiliation: Department of Chemistry, University of California, Davis, CA 95616, USA.
authors.forename: Valentin
authors.initials: V
authors.lastname: Lulevich
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Zimmer
authors.forename: Hyun-seok
authors.initials: HS
authors.lastname: Hong
authors.forename: Lee-way
authors.initials: LW
authors.lastname: Jin
authors.forename: Gang-yu
authors.initials: GY
authors.lastname: Liu
mesh_terms: 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
chemical_list: D016229:Amyloid beta-Peptides