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Cortical cell stiffness is independent of substrate mechanics

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Rheinlaender_2020_NatMaterials_corticalcell_AAM.pdf (1.089Mb)
Date
09/2020
Author
Rheinlaender, Johannes
Dimitracopoulos, Andrea
Wallmeyer, Bernhard
Kronenberg, Nils M.
Chalut, Kevin J.
Gather, Malte C.
Betz, Timo
Charras, Guillaume
Franze, Kristian
Keywords
Cell stiffness
Stiffening
AFM
Susbtrate stiffness
Polyacrylamide
ERISM
QC Physics
QH301 Biology
Chemistry(all)
Materials Science(all)
Mechanical Engineering
Mechanics of Materials
Condensed Matter Physics
DAS
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Abstract
Cortical stiffness is an important cellular property that changes during migration, adhesion and growth. Previous atomic force microscopy (AFM) indentation measurements of cells cultured on deformable substrates have suggested that cells adapt their stiffness to that of their surroundings. Here we show that the force applied by AFM to a cell results in a significant deformation of the underlying substrate if this substrate is softer than the cell. This ‘soft substrate effect’ leads to an underestimation of a cell’s elastic modulus when analysing data using a standard Hertz model, as confirmed by finite element modelling and AFM measurements of calibrated polyacrylamide beads, microglial cells and fibroblasts. To account for this substrate deformation, we developed a ‘composite cell–substrate model’. Correcting for the substrate indentation revealed that cortical cell stiffness is largely independent of substrate mechanics, which has major implications for our interpretation of many physiological and pathological processes.
Citation
Rheinlaender , J , Dimitracopoulos , A , Wallmeyer , B , Kronenberg , N M , Chalut , K J , Gather , M C , Betz , T , Charras , G & Franze , K 2020 , ' Cortical cell stiffness is independent of substrate mechanics ' , Nature Materials , vol. 19 , pp. 1019–1025 . https://doi.org/10.1038/s41563-020-0684-x
Publication
Nature Materials
Status
Peer reviewed
DOI
https://doi.org/10.1038/s41563-020-0684-x
ISSN
1476-1122
Type
Journal article
Rights
Copyright © 2020 the Author(s) under exclusive licence to Springer Nature Limited. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1038/s41563-020-0684-x.
Description
Funding: We acknowledge funding from the German Science Foundation (DFG grant numbers RH 147/1-1 to J.R., EXC 1003 CiM to T.B.), the Herchel Smith Foundation (postdoctoral fellowship to A.D.), the Royal Society (University Research Fellowship to K.J.C.), the UK EPSRC (programme grant number EP/P030017/1 to M.C.G.), the Human Frontier Science Program (HFSP grant number RGP0018/2017 to T.B.), the European Research Council (consolidator grant numbers 772798 to K.J.C., 771201 to T.B., 647186 to G.C. and 772426 to K.F.), and the UK BBSRC (equipment grant number BB/R000042/1 to G.C. and research project grant number BB/N006402/1 to K.F.).
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/21082

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