Optical‐mechanical signatures of cancer cells based on fluctuation profiles measured by interferometry

We propose to establish a cancer biomarker based on the unique optical-mechanical signatures of cancer cells measured in a noncontact, label-free manner by optical interferometry. Using wide-field interferometric phase microscopy (IPM), implemented by a portable, off-axis, common-path and low-coherence interferometric module, we quantitatively measured the time-dependent, nanometer-scale optical thickness fluctuation maps of live cells in vitro. We found that cancer cells fluctuate significantly more than healthy cells, and that metastatic cancer cells fluctuate significantly more than primary cancer cells. Atomic force microscopy (AFM) measurements validated the results. Our study shows the potential of IPM as a simple clinical tool for aiding in diagnosis and monitoring of cancer.

[1]  Pinhas Girshovitz,et al.  Generalized cell morphological parameters based on interferometric phase microscopy and their application to cell life cycle characterization , 2012, Biomedical optics express.

[2]  K. Bhadriraju,et al.  Extracellular matrix- and cytoskeleton-dependent changes in cell shape and stiffness. , 2002, Experimental cell research.

[3]  Yongkeun Park,et al.  Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum , 2008, Proceedings of the National Academy of Sciences.

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

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

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

[7]  P. Marquet,et al.  Comparative study of human erythrocytes by digital holographic microscopy, confocal microscopy, and impedance volume analyzer , 2008, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[8]  Haniel Gabai,et al.  Dual-channel low-coherence interferometry and its application to quantitative phase imaging of fingerprints. , 2012, Optics express.

[9]  Joseph Rosen Holography, Research and Technologies , 2011 .

[10]  Ueli Aebi,et al.  Dynamic elastic modulus of porcine articular cartilage determined at two different levels of tissue organization by indentation-type atomic force microscopy. , 2004, Biophysical journal.

[11]  C Rotsch,et al.  Drug-induced changes of cytoskeletal structure and mechanics in fibroblasts: an atomic force microscopy study. , 2000, Biophysical journal.

[12]  Pietro Ferraro,et al.  Compensation of the inherent wave front curvature in digital holographic coherent microscopy for quantitative phase-contrast imaging. , 2003, Applied optics.

[13]  Gabriel Popescu,et al.  Imaging red blood cell dynamics by quantitative phase microscopy. , 2008, Blood cells, molecules & diseases.

[14]  N. Arber,et al.  Celecoxib But Not Rofecoxib Inhibits the Growth of Transformed Cells in Vitro , 2004, Clinical Cancer Research.

[15]  Steve Pawlizak,et al.  Are biomechanical changes necessary for tumor progression , 2010 .

[16]  Björn Kemper,et al.  Simplified approach for quantitative digital holographic phase contrast imaging of living cells. , 2011, Journal of biomedical optics.

[17]  Hao Zhang,et al.  Abstract 1: Mcl-1 downregulation plays a crucial role in the synergistic anticancer activities between PI-3 kinase inhibitors and histone deacetylase inhibitors in primary NSCLC tumorsin vitroandin vivo , 2011 .

[18]  Michael Beil,et al.  Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells , 2003, Nature Cell Biology.

[19]  Natan T Shaked,et al.  Quantitative phase microscopy of biological samples using a portable interferometer. , 2012, Optics letters.

[20]  Manfred Radmacher,et al.  Direct, high-resolution measurement of furrow stiffening during division of adherent cells , 2001, Nature Cell Biology.

[21]  John F. Canny,et al.  A Computational Approach to Edge Detection , 1986, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[22]  J. Gass,et al.  Phase imaging without 2pi ambiguity by multiwavelength digital holography. , 2003, Optics letters.

[23]  H. Verschueren,et al.  Direct correlation between cell membrane fluctuations, cell filterability and the metastatic potential of lymphoid cell lines. , 1994, Biochemical and biophysical research communications.

[24]  Pinhas Girshovitz,et al.  Optical phase nanoscopy in red blood cells using low-coherence spectroscopy , 2012, Journal of biomedical optics.

[25]  S. Suresh,et al.  Cell and molecular mechanics of biological materials , 2003, Nature materials.

[26]  N. Shaked,et al.  Compact and portable low-coherence interferometer with off-axis geometry for quantitative phase microscopy and nanoscopy. , 2013, Optics express.

[27]  Bernard Nysten,et al.  Nanoscale mapping of the elasticity of microbial cells by atomic force microscopy , 2003 .

[28]  Hanina Hibshoosh,et al.  CD24 is a new oncogene, early at the multistep process of colorectal cancer carcinogenesis. , 2006, Gastroenterology.

[29]  G. Piazza,et al.  A K-ras oncogene increases resistance to sulindac-induced apoptosis in rat enterocytes. , 1997, Gastroenterology.

[30]  Subra Suresh,et al.  Biomechanics and biophysics of cancer cells. , 2007, Acta biomaterialia.

[31]  Subra Suresh,et al.  Viscoelasticity of the human red blood cell , 2006, American journal of physiology. Cell physiology.

[32]  Richard Superfine,et al.  Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines. , 2011, Cancer research.

[33]  G. Truskey,et al.  Quantitative microscopy and nanoscopy of sickle red blood cells performed by wide field digital interferometry. , 2011, Journal of biomedical optics.

[34]  M. Sheetz,et al.  Local force and geometry sensing regulate cell functions , 2006, Nature Reviews Molecular Cell Biology.

[35]  P K Hansma,et al.  Measuring the viscoelastic properties of human platelets with the atomic force microscope. , 1996, Biophysical journal.

[36]  A. Vasanji,et al.  Polarization of plasma membrane microviscosity during endothelial cell migration. , 2004, Developmental cell.

[37]  Axel Niendorf,et al.  Passive and active single-cell biomechanics: a new perspective in cancer diagnosis , 2009 .

[38]  B. Shalmon,et al.  CXCL10 promotes invasion-related properties in human colorectal carcinoma cells. , 2007, Cancer research.

[39]  K. Zänker,et al.  Differences in the migration capacity of primary human colon carcinoma cells (SW480) and their lymph node metastatic derivatives (SW620). , 1998, Cancer letters.

[40]  I. Weinstein,et al.  Increased expression of cyclin D1 and the Rb tumor suppressor gene in c-K-ras transformed rat enterocytes. , 1996, Oncogene.

[41]  Gabriel Popescu,et al.  Coherence properties of red blood cell membrane motions. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.