Atomic force microscopy-based microrheology reveals significant differences in the viscoelastic response between malign and benign cell lines

Mechanical phenotyping of cells by atomic force microscopy (AFM) was proposed as a novel tool in cancer cell research as cancer cells undergo massive structural changes, comprising remodelling of the cytoskeleton and changes of their adhesive properties. In this work, we focused on the mechanical properties of human breast cell lines with different metastatic potential by AFM-based microrheology experiments. Using this technique, we are not only able to quantify the mechanical properties of living cells in the context of malignancy, but we also obtain a descriptor, namely the loss tangent, which provides model-independent information about the metastatic potential of the cell line. Including also other cell lines from different organs shows that the loss tangent (G″/G′) increases generally with the metastatic potential from MCF-10A representing benign cells to highly malignant MDA-MB-231 cells.

[1]  S. Chizhik,et al.  Atomic force microscopy probing of cell elasticity. , 2007, Micron.

[2]  R. Reeves,et al.  Tumor suppressor in lung cancer 1 (TSLC1) alters tumorigenic growth properties and gene expression , 2005, Molecular Cancer.

[3]  James K. Gimzewski,et al.  Applicability of AFM in cancer detection , 2009 .

[4]  G. G. Bilodeau,et al.  Regular Pyramid Punch Problem , 1992 .

[5]  Peter Grütter,et al.  Probing the viscoelastic behavior of cultured airway smooth muscle cells with atomic force microscopy: stiffening induced by contractile agonist. , 2005, Biophysical journal.

[6]  J. Rao,et al.  Nanomechanical analysis of cells from cancer patients. , 2007, Nature nanotechnology.

[7]  S. Bornstein,et al.  Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: Antiproliferative effects of peptide analogues , 2009, Proceedings of the National Academy of Sciences.

[8]  Stefan Schinkinger,et al.  Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. , 2005, Biophysical journal.

[9]  S. Timoshenko,et al.  Theory of elasticity , 1975 .

[10]  Christopher S. Poultney,et al.  A physical sciences network characterization of non-tumorigenic and metastatic cells , 2013, Scientific Reports.

[11]  Sanjay Kumar,et al.  Mechanics, malignancy, and metastasis: The force journey of a tumor cell , 2009, Cancer and Metastasis Reviews.

[12]  F. MacKintosh,et al.  Scanning probe-based frequency-dependent microrheology of polymer gels and biological cells. , 2000, Physical review letters.

[13]  Albrecht Ott,et al.  Rheological properties of the Eukaryotic cell cytoskeleton , 2007 .

[14]  Paul J. Williams,et al.  The bisphosphonate ibandronate promotes apoptosis in MDA-MB-231 human breast cancer cells in bone metastases. , 2001, Cancer research.

[15]  Małgorzata Lekka,et al.  Applicability of AFM in cancer detection. , 2009, Nature nanotechnology.

[16]  Gerber,et al.  Atomic Force Microscope , 2020, Definitions.

[17]  Ben Fabry,et al.  Active soft glassy rheology of adherent cells , 2009 .

[18]  D. Navajas,et al.  Scaling the microrheology of living cells. , 2001, Physical review letters.

[19]  Daniel A Fletcher,et al.  Force microscopy of nonadherent cells: a comparison of leukemia cell deformability. , 2006, Biophysical journal.

[20]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[21]  R. Lal,et al.  Dynamic micromechanical properties of cultured rat atrial myocytes measured by atomic force microscopy. , 1995, The American journal of physiology.

[22]  Ben Fabry,et al.  Microrheology of human lung epithelial cells measured by atomic force microscopy. , 2003, Biophysical journal.

[23]  L. Liotta,et al.  Formation of metastasis by human breast carcinoma cells (MCF-7) in nude mice. , 1980, Cancer letters.

[24]  J. Dukes,et al.  The MDCK variety pack: choosing the right strain , 2011, BMC Cell Biology.

[25]  Chwee Teck Lim,et al.  Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria. , 2005, Acta biomaterialia.

[26]  F. MacKintosh,et al.  Nonequilibrium Mechanics of Active Cytoskeletal Networks , 2007, Science.

[27]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[28]  E. Paluch,et al.  Mechanics and regulation of cell shape during the cell cycle. , 2011, Results and problems in cell differentiation.

[29]  Erik Sahai,et al.  The actin cytoskeleton in cancer cell motility , 2009, Clinical & Experimental Metastasis.

[30]  H. Yamasaki,et al.  Connexin32 as a tumor suppressor gene in a metastatic renal cell carcinoma cell line , 2005, Oncogene.

[31]  Rheological constitutive equation for a model of soft glassy materials , 1997, cond-mat/9712001.

[32]  Z. Stachura,et al.  Elasticity of normal and cancerous human bladder cells studied by scanning force microscopy , 1999, European Biophysics Journal.

[33]  J. Alcaraz,et al.  Correction of Microrheological Measurements of Soft Samples with Atomic Force Microscopy for the Hydrodynamic Drag on the Cantilever , 2002 .

[34]  Gang Zhang,et al.  Mechanical properties of hepatocellular carcinoma cells. , 2002, World journal of gastroenterology.

[35]  T. E. Schroeder The contractile ring. II. Determining its brief existence, volumetric changes, and vital role in cleaving Arbacia eggs. , 1972 .