1. Cortical cell stiffness is independent of substrate mechanics
- Author
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Nils M. Kronenberg, Kristian Franze, Malte C. Gather, Timo Betz, Guillaume Charras, Bernhard Wallmeyer, Johannes Rheinlaender, Andrea Dimitracopoulos, Kevin J. Chalut, Rheinlaender, Johannes [0000-0002-1976-9245], Kronenberg, Nils M [0000-0001-6386-3848], Gather, Malte C [0000-0002-4857-5562], Betz, Timo [0000-0002-1548-0655], Charras, Guillaume [0000-0002-7902-0279], Franze, Kristian [0000-0002-8425-7297], Apollo - University of Cambridge Repository, EPSRC, University of St Andrews. School of Physics and Astronomy, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Centre for Biophotonics, and University of St Andrews. Biomedical Sciences Research Complex
- Subjects
Polyacrylamide ,Chemistry(all) ,QH301 Biology ,Composite number ,02 engineering and technology ,Microscopy, Atomic Force ,ERISM ,01 natural sciences ,Substrate Specificity ,Cell stiffness ,Indentation ,Microscopy ,Susbtrate stiffness ,General Materials Science ,R2C ,QC ,Cerebral Cortex ,0303 health sciences ,Stiffness ,Cell Differentiation ,Mechanics ,Adhesion ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Finite element method ,Stiffening ,Mechanics of Materials ,AFM ,Deformation (engineering) ,medicine.symptom ,BDC ,polyacrylamide ,0210 nano-technology ,cell stiffness ,Materials science ,substrate stiffness ,010402 general chemistry ,Article ,03 medical and health sciences ,QH301 ,Materials Science(all) ,Elastic Modulus ,medicine ,stiffening ,Elastic modulus ,030304 developmental biology ,Mechanical Engineering ,technology, industry, and agriculture ,Substrate (chemistry) ,DAS ,General Chemistry ,0104 chemical sciences ,body regions ,QC Physics - Abstract
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.). 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. Postprint
- Published
- 2020
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