Document Detail


Single-cell mechanics provides a sensitive and quantitative means for probing amyloid-beta peptide and neuronal cell interactions.
MedLine Citation:
PMID:  20643929     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Valentin Lulevich; Christopher C Zimmer; Hyun-seok Hong; Lee-way Jin; Gang-yu Liu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-19
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-04     Completed Date:  2010-09-08     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13872-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amyloid beta-Peptides / chemistry*
Animals
Cell Communication*
Cell Line
Mice
Neurons / chemistry*,  physiology
Nonlinear Dynamics
Protein Multimerization
Grant Support
ID/Acronym/Agency:
1R01 AG025500/AG/NIA NIH HHS; 1R21 AG031362/AG/NIA NIH HHS; 1R21 GM077850-01/GM/NIGMS NIH HHS; AG010129/AG/NIA NIH HHS; P30 AG010129/AG/NIA NIH HHS; P30 AG010129-20/AG/NIA NIH HHS; R21 GM077850/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides
Comments/Corrections

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