期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：31
页码：13872-13877
DOI：10.1073/pnas.1008341107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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-{beta}42 (A{beta}42) protein treatment. A{beta}42 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 A{beta}42 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 A{beta}42 oligomers, which have been considered the prime suspect for initiating neuronal dysfunction in Alzheimer's disease.
