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

Proceedings of the National Academy of Sciences of the United States of America
Valentin LulevichGang-yu Liu

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.

References

Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·A Lorenzo, B A Yankner
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·N ArispeH B Pollard
Sep 25, 2001·Cellular and Molecular Neurobiology·J I KourieP Farrelly
May 29, 2003·Current Drug Targets. CNS and Neurological Disorders·Patrice Talaga, Luc Quéré
Aug 12, 2003·Cell Calcium·Mark P Mattson, Sic L Chan
Feb 18, 2004·Current Protein & Peptide Science·Yann Verdier, Botond Penke
May 27, 2004·Journal of Peptide Science : an Official Publication of the European Peptide Society·Yann VerdierBotond Penke
Aug 6, 2004·Nature·Mark P Mattson
Feb 22, 2005·The Journal of Biological Chemistry·Angelo DemuroCharles G Glabe
Apr 20, 2005·Langmuir : the ACS Journal of Surfaces and Colloids·Valentin V Lulevich, Olga I Vinogradova
Jul 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Arjan QuistRatnesh Lal
Aug 2, 2005·Biophysical Journal·Kris Noel DahlDennis E Discher
Oct 8, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Casper CaspersenShi Du Yan
Mar 17, 2006·Nature·Sylvain LesnéKaren H Ashe
Apr 14, 2006·Current Alzheimer Research·Yuanbin Liu, David Schubert
Apr 21, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Claudia G AlmeidaGunnar K Gouras
Sep 6, 2006·Langmuir : the ACS Journal of Surfaces and Colloids·Valentin LulevichGang-Yu Liu
Jun 7, 2007·Nature Reviews. Neuroscience·Frank M LaFerlaSalvatore Oddo
Oct 24, 2007·Journal of Neurochemistry·Izumi MaezawaLee-Way Jin
Aug 30, 2008·The Journal of Biological Chemistry·Charles G Glabe
Apr 16, 2009·The Journal of Physical Chemistry. B·Valentin LulevichGang-Yu Liu
Jun 16, 2009·Journal of Molecular Biology·Erene W MinaRakez Kayed
Mar 10, 2010·The Journal of Biological Chemistry·Angelo DemuroGrace E Stutzmann

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Citations

Aug 28, 2012·Langmuir : the ACS Journal of Surfaces and Colloids·Wei WangNongjian Tao
Nov 19, 2013·Nano Letters·Xi XieNicholas A Melosh
Aug 31, 2011·Proceedings of the National Academy of Sciences of the United States of America·Christopher AgnewR Leo Brady
Jun 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Anthony W P FitzpatrickAhmed H Zewail
Jun 8, 2012·Cold Spring Harbor Perspectives in Medicine·Colin L Masters, Dennis J Selkoe
May 7, 2013·Annual Review of Biomedical Engineering·Kristian FranzeJochen Guck
Aug 8, 2013·International Journal of Molecular Sciences·Elise Spedden, Cristian Staii
Jul 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Therese W HerlingTuomas P J Knowles
Mar 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Anthony W P FitzpatrickAhmed H Zewail
Aug 24, 2010·Ultramicroscopy·Valentin LulevichGang-yu Liu
Jun 16, 2015·Frontiers in Neuroscience·Donghui ZhuSholpan Askarova
Jun 25, 2015·BioMed Research International·Wei HuWei J Chen
Jun 25, 2016·BMC Biophysics·Yareni A AyalaH Moysés Nussenzveig
Aug 28, 2014·PloS One·Austin SendekDaniel L Cox
Nov 18, 2016·European Biophysics Journal : EBJ·Zhuoyang LuJiankang Liu
Jan 20, 2017·Lab on a Chip·Jitao ZhangGiuliano Scarcelli
Jul 15, 2015·Soft Matter·Galyna GorbenkoHiroyuki Saito
Jun 11, 2015·Translational Neuroscience·Maja Jazvinšćak JembrekSuzana Šegota
May 2, 2020·The European Journal of Neuroscience·Chloe M HallGraham K Sheridan
Mar 31, 2012·Journal of Neuroscience Research·Andrei P Sommer
Oct 3, 2020·International Journal of Molecular Sciences·Vivian Alonso-GarciaFernando A Fierro
May 30, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Martina Pannuzzo
Jan 15, 2014·The Journal of Physical Chemistry. B·Christopher C ZimmerGang-yu Liu
Dec 12, 2020·The Journal of Physical Chemistry. B·Evgeny OgorodnikGang-Yu Liu

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