Abstract

We explore the dynamics of cancer cell filopodia of diameters around 200 nm by using super-resolution bright-field optical microscopy. The high contrast required by the super-resolution image-restoration process is from the nanometer topographic sensitivity of non-interferometric widefield optical profilometry, rather than fluorescence labeling. Because the image-acquisition rate of this bright-field system is 20 frames/min, fast cellular dynamics can be captured and then analyzed. We successfully observe the growth and activities of the filopodia of a CL1–0 lung cancer cell. In the culturing condition, we measure that the filopodia exhibit an average elongation rate of 90 nm/sec, and an average shrinkage rate of 75 nm/sec. With the treatment of epidermal growth factor, the elongation and shrinkage rates increase to 110 nm/sec and 100 nm/sec respectively. We also find that the treatment of epidermal growth factor raises the number of filopodia by nearly a factor of 2, which implies enhancement of cell motility.

© 2007 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
    [CrossRef] [PubMed]
  2. O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
    [CrossRef] [PubMed]
  3. L. J. Kleinsmith, and V. M. Kish, Principles of Cell and Molecular Biology (HarperCollins College Publishers, New York, 1995).
  4. J. V. Small, K. Rottner, P. Hahne, and K. I. Anderson, "Visualising the actin cytoskeleton," Microsc. Res. Tech. 47, 3-17 (1999).
    [CrossRef] [PubMed]
  5. W. A. Carrington, R. M. Lynch, E. D. W. Moore, G. Isenberg, K. E. Fogarty, and F. S. Fay, "Super resolution three-dimensional images of fluorescence in cells with minimal light exposure," Science 268, 1483-1486 (1995).
    [CrossRef] [PubMed]
  6. D. S. Lidke, K. A. Lidke, B. Rieger, T. M. Jovin, and D. J. Arndt-Jovin, "Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors," J. Cell Biol. 170, 619-626 (2005).
    [CrossRef] [PubMed]
  7. M. M. Knight, S. R. Roberts, D. A. Lee, and D. L. Bader, "Live cell imaging using confocal microscopy induces intracellular calcium transients and cell death," Am. J. Physiol. Cell Physiol. 284, C1083-C1089 (2003).
    [PubMed]
  8. S. Landry, P. L. McGhee, R. J. Girardin, and W. J. Keeler, "Monitoring live cell viability: Comparative study of fluorescence, oblique incidence reflection and phase contrast microscopy imaging techniques," Opt. Express 12, 5754-5759 (2004).
    [CrossRef] [PubMed]
  9. C.-H. Lee, H.-Y. Mong, and W.-C. Lin, "Noninterferometric wide-field optical profilometry with nanometer depth resolution," Opt. Lett. 27, 1773-1775 (2002).
    [CrossRef]
  10. M. A. A. Neil, R. Juskaitis, and T. Wilson, "Method of obtaining optical sectioning by using structured light in a conventional microscope," Opt. Lett. 22, 1905-1907 (1997).
    [CrossRef]
  11. S.-W. Huang, H.-Y. Mong, and C.-H. Lee, "Super-resolution bright-field optical microscopy based on nanometer topographic contrast," Microsc. Res. Tech. 65, 180-185 (2004).
    [CrossRef]
  12. J. C. Russ, The Image Processing Handbook (CRC Press, Boca Raton, 1995), Chap. 3.
  13. C.-C. Wang, J.-Y. Lin, and C.-H. Lee, "Membrane ripples of a living cell measured by non-interferometric widefield optical profilometry," Opt. Express 13, 10665-10672 (2005).
    [CrossRef] [PubMed]
  14. M. Schrader, S. W. Hell, and H. T. M. van der Voort, "Potential of confocal microscopes to resolve in the 50-100 nm range," Appl. Phys. Lett. 69, 3644-3646 (1996).
    [CrossRef]
  15. J.-A. Conchello, "Superresolution and convergence properties of the expectation-maximization algorithm for maximum-likelihood deconvolution of incoherent images," J. Opt. Soc. Am. A 15, 2609-2619 (1998).
    [CrossRef]
  16. C.-H. Lee, H.-Y. Chiang, and H.-Y. Mong, "Sub-diffraction-limit imaging based on the topographic contrast of differential confocal microscopy," Opt. Lett. 28, 1772-1774 (2003).
    [CrossRef] [PubMed]
  17. A. Wells, "EGF receptor," Int. J. Biochem. Cell Biol. 31, 637-643 (1999).
    [CrossRef] [PubMed]

2005 (3)

O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
[CrossRef] [PubMed]

D. S. Lidke, K. A. Lidke, B. Rieger, T. M. Jovin, and D. J. Arndt-Jovin, "Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors," J. Cell Biol. 170, 619-626 (2005).
[CrossRef] [PubMed]

C.-C. Wang, J.-Y. Lin, and C.-H. Lee, "Membrane ripples of a living cell measured by non-interferometric widefield optical profilometry," Opt. Express 13, 10665-10672 (2005).
[CrossRef] [PubMed]

2004 (2)

2003 (2)

M. M. Knight, S. R. Roberts, D. A. Lee, and D. L. Bader, "Live cell imaging using confocal microscopy induces intracellular calcium transients and cell death," Am. J. Physiol. Cell Physiol. 284, C1083-C1089 (2003).
[PubMed]

C.-H. Lee, H.-Y. Chiang, and H.-Y. Mong, "Sub-diffraction-limit imaging based on the topographic contrast of differential confocal microscopy," Opt. Lett. 28, 1772-1774 (2003).
[CrossRef] [PubMed]

2002 (1)

2001 (1)

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

1999 (2)

J. V. Small, K. Rottner, P. Hahne, and K. I. Anderson, "Visualising the actin cytoskeleton," Microsc. Res. Tech. 47, 3-17 (1999).
[CrossRef] [PubMed]

A. Wells, "EGF receptor," Int. J. Biochem. Cell Biol. 31, 637-643 (1999).
[CrossRef] [PubMed]

1998 (1)

1997 (1)

1996 (1)

M. Schrader, S. W. Hell, and H. T. M. van der Voort, "Potential of confocal microscopes to resolve in the 50-100 nm range," Appl. Phys. Lett. 69, 3644-3646 (1996).
[CrossRef]

1995 (1)

W. A. Carrington, R. M. Lynch, E. D. W. Moore, G. Isenberg, K. E. Fogarty, and F. S. Fay, "Super resolution three-dimensional images of fluorescence in cells with minimal light exposure," Science 268, 1483-1486 (1995).
[CrossRef] [PubMed]

Anderson, K. I.

J. V. Small, K. Rottner, P. Hahne, and K. I. Anderson, "Visualising the actin cytoskeleton," Microsc. Res. Tech. 47, 3-17 (1999).
[CrossRef] [PubMed]

Arndt-Jovin, D. J.

D. S. Lidke, K. A. Lidke, B. Rieger, T. M. Jovin, and D. J. Arndt-Jovin, "Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors," J. Cell Biol. 170, 619-626 (2005).
[CrossRef] [PubMed]

Bader, D. L.

M. M. Knight, S. R. Roberts, D. A. Lee, and D. L. Bader, "Live cell imaging using confocal microscopy induces intracellular calcium transients and cell death," Am. J. Physiol. Cell Physiol. 284, C1083-C1089 (2003).
[PubMed]

Baibakov, B.

O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
[CrossRef] [PubMed]

Carrington, W. A.

W. A. Carrington, R. M. Lynch, E. D. W. Moore, G. Isenberg, K. E. Fogarty, and F. S. Fay, "Super resolution three-dimensional images of fluorescence in cells with minimal light exposure," Science 268, 1483-1486 (1995).
[CrossRef] [PubMed]

Chang, Y.-L.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Chen, J. J. W.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Chiang, H.-Y.

Choti, M. A.

O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
[CrossRef] [PubMed]

Conchello, J.-A.

Donowitz, M.

O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
[CrossRef] [PubMed]

Elowsky, C.

O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
[CrossRef] [PubMed]

Fay, F. S.

W. A. Carrington, R. M. Lynch, E. D. W. Moore, G. Isenberg, K. E. Fogarty, and F. S. Fay, "Super resolution three-dimensional images of fluorescence in cells with minimal light exposure," Science 268, 1483-1486 (1995).
[CrossRef] [PubMed]

Fogarty, K. E.

W. A. Carrington, R. M. Lynch, E. D. W. Moore, G. Isenberg, K. E. Fogarty, and F. S. Fay, "Super resolution three-dimensional images of fluorescence in cells with minimal light exposure," Science 268, 1483-1486 (1995).
[CrossRef] [PubMed]

Girardin, R. J.

Hahne, P.

J. V. Small, K. Rottner, P. Hahne, and K. I. Anderson, "Visualising the actin cytoskeleton," Microsc. Res. Tech. 47, 3-17 (1999).
[CrossRef] [PubMed]

Hell, S. W.

M. Schrader, S. W. Hell, and H. T. M. van der Voort, "Potential of confocal microscopes to resolve in the 50-100 nm range," Appl. Phys. Lett. 69, 3644-3646 (1996).
[CrossRef]

Hong, T.-M.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Huang, S.-W.

S.-W. Huang, H.-Y. Mong, and C.-H. Lee, "Super-resolution bright-field optical microscopy based on nanometer topographic contrast," Microsc. Res. Tech. 65, 180-185 (2004).
[CrossRef]

Isenberg, G.

W. A. Carrington, R. M. Lynch, E. D. W. Moore, G. Isenberg, K. E. Fogarty, and F. S. Fay, "Super resolution three-dimensional images of fluorescence in cells with minimal light exposure," Science 268, 1483-1486 (1995).
[CrossRef] [PubMed]

Jovin, T. M.

D. S. Lidke, K. A. Lidke, B. Rieger, T. M. Jovin, and D. J. Arndt-Jovin, "Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors," J. Cell Biol. 170, 619-626 (2005).
[CrossRef] [PubMed]

Juskaitis, R.

Kane, A.

O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
[CrossRef] [PubMed]

Keeler, W. J.

Knight, M. M.

M. M. Knight, S. R. Roberts, D. A. Lee, and D. L. Bader, "Live cell imaging using confocal microscopy induces intracellular calcium transients and cell death," Am. J. Physiol. Cell Physiol. 284, C1083-C1089 (2003).
[PubMed]

Kovbasnjuk, O.

O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
[CrossRef] [PubMed]

Landry, S.

Lee, C.-H.

Lee, D. A.

M. M. Knight, S. R. Roberts, D. A. Lee, and D. L. Bader, "Live cell imaging using confocal microscopy induces intracellular calcium transients and cell death," Am. J. Physiol. Cell Physiol. 284, C1083-C1089 (2003).
[PubMed]

Lee, Y.-C.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Lidke, D. S.

D. S. Lidke, K. A. Lidke, B. Rieger, T. M. Jovin, and D. J. Arndt-Jovin, "Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors," J. Cell Biol. 170, 619-626 (2005).
[CrossRef] [PubMed]

Lidke, K. A.

D. S. Lidke, K. A. Lidke, B. Rieger, T. M. Jovin, and D. J. Arndt-Jovin, "Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors," J. Cell Biol. 170, 619-626 (2005).
[CrossRef] [PubMed]

Lin, J.-Y.

Lin, W.-C.

Lynch, R. M.

W. A. Carrington, R. M. Lynch, E. D. W. Moore, G. Isenberg, K. E. Fogarty, and F. S. Fay, "Super resolution three-dimensional images of fluorescence in cells with minimal light exposure," Science 268, 1483-1486 (1995).
[CrossRef] [PubMed]

McGhee, P. L.

Mong, H.-Y.

Moore, E. D. W.

W. A. Carrington, R. M. Lynch, E. D. W. Moore, G. Isenberg, K. E. Fogarty, and F. S. Fay, "Super resolution three-dimensional images of fluorescence in cells with minimal light exposure," Science 268, 1483-1486 (1995).
[CrossRef] [PubMed]

Mourtazina, R.

O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
[CrossRef] [PubMed]

Neil, M. A. A.

Peck, K.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Rieger, B.

D. S. Lidke, K. A. Lidke, B. Rieger, T. M. Jovin, and D. J. Arndt-Jovin, "Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors," J. Cell Biol. 170, 619-626 (2005).
[CrossRef] [PubMed]

Roberts, S. R.

M. M. Knight, S. R. Roberts, D. A. Lee, and D. L. Bader, "Live cell imaging using confocal microscopy induces intracellular calcium transients and cell death," Am. J. Physiol. Cell Physiol. 284, C1083-C1089 (2003).
[PubMed]

Rottner, K.

J. V. Small, K. Rottner, P. Hahne, and K. I. Anderson, "Visualising the actin cytoskeleton," Microsc. Res. Tech. 47, 3-17 (1999).
[CrossRef] [PubMed]

Schrader, M.

M. Schrader, S. W. Hell, and H. T. M. van der Voort, "Potential of confocal microscopes to resolve in the 50-100 nm range," Appl. Phys. Lett. 69, 3644-3646 (1996).
[CrossRef]

Shih, J.-Y.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Small, J. V.

J. V. Small, K. Rottner, P. Hahne, and K. I. Anderson, "Visualising the actin cytoskeleton," Microsc. Res. Tech. 47, 3-17 (1999).
[CrossRef] [PubMed]

van der Voort, H. T. M.

M. Schrader, S. W. Hell, and H. T. M. van der Voort, "Potential of confocal microscopes to resolve in the 50-100 nm range," Appl. Phys. Lett. 69, 3644-3646 (1996).
[CrossRef]

Wang, C.-C.

Wang, T.

O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
[CrossRef] [PubMed]

Wells, A.

A. Wells, "EGF receptor," Int. J. Biochem. Cell Biol. 31, 637-643 (1999).
[CrossRef] [PubMed]

Wilson, T.

Wu, C.-W.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Yang, P.-C.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Yang, S.-C.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Yu, C.-J.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Yuan, A.

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

Am. J. Physiol. Cell Physiol. (1)

M. M. Knight, S. R. Roberts, D. A. Lee, and D. L. Bader, "Live cell imaging using confocal microscopy induces intracellular calcium transients and cell death," Am. J. Physiol. Cell Physiol. 284, C1083-C1089 (2003).
[PubMed]

Appl. Phys. Lett. (1)

M. Schrader, S. W. Hell, and H. T. M. van der Voort, "Potential of confocal microscopes to resolve in the 50-100 nm range," Appl. Phys. Lett. 69, 3644-3646 (1996).
[CrossRef]

Int. J. Biochem. Cell Biol. (1)

A. Wells, "EGF receptor," Int. J. Biochem. Cell Biol. 31, 637-643 (1999).
[CrossRef] [PubMed]

J. Cell Biol. (1)

D. S. Lidke, K. A. Lidke, B. Rieger, T. M. Jovin, and D. J. Arndt-Jovin, "Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors," J. Cell Biol. 170, 619-626 (2005).
[CrossRef] [PubMed]

J. Natl. Cancer Inst. (1)

J.-Y. Shih, S.-C. Yang, T.-M. Hong, A. Yuan, J. J. W. Chen, C.-J. Yu, Y.-L. Chang, Y.-C. Lee, K. Peck, C.-W. Wu, and P.-C. Yang, "Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells," J. Natl. Cancer Inst. 93, 1392-1400 (2001).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A (1)

Microsc. Res. Tech. (2)

J. V. Small, K. Rottner, P. Hahne, and K. I. Anderson, "Visualising the actin cytoskeleton," Microsc. Res. Tech. 47, 3-17 (1999).
[CrossRef] [PubMed]

S.-W. Huang, H.-Y. Mong, and C.-H. Lee, "Super-resolution bright-field optical microscopy based on nanometer topographic contrast," Microsc. Res. Tech. 65, 180-185 (2004).
[CrossRef]

Opt. Express (2)

Opt. Lett. (3)

Proc. Natl. Acad. Sci. U.S.A. (1)

O. Kovbasnjuk, R. Mourtazina, B. Baibakov, T. Wang, C. Elowsky, M. A. Choti, A. Kane, and M. Donowitz, "The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer," Proc. Natl. Acad. Sci. U.S.A. 102, 19087-19092 (2005).
[CrossRef] [PubMed]

Science (1)

W. A. Carrington, R. M. Lynch, E. D. W. Moore, G. Isenberg, K. E. Fogarty, and F. S. Fay, "Super resolution three-dimensional images of fluorescence in cells with minimal light exposure," Science 268, 1483-1486 (1995).
[CrossRef] [PubMed]

Other (2)

L. J. Kleinsmith, and V. M. Kish, Principles of Cell and Molecular Biology (HarperCollins College Publishers, New York, 1995).

J. C. Russ, The Image Processing Handbook (CRC Press, Boca Raton, 1995), Chap. 3.

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (7)

Fig. 1.
Fig. 1.

Setup of the non-interferometric widefield optical profilometry system.

Fig. 2.
Fig. 2.

Bright-field reflection image of a CL1–0 lung cancer cell. Zoom-in images of the region enclosed by a dashed square are shown in Fig. 3.

Fig. 3.
Fig. 3.

(a). Bright-field reflection image of the edge of a CL1–0 lung cancer cell. (b) NIWOP topography. NIWOP greatly improves the contrast of filopodia (indicated by the arrows).

Fig. 4.
Fig. 4.

Images after the super-resolution image restoration. (a) Bright-field reflection image. (b) NIWOP topography.

Fig. 5.
Fig. 5.

(a). Raw NIWOP image of a region with dense filopodia. (b) Restored NIWOP image showing 5 filopodia. (c) The line profiles across the filopodium indicated by the dashed lines in panels (a) and (b). The 10–90% intensity edge response of the restored image is about 120 nm.

Fig. 6.
Fig. 6.

NIWOP images of a CL1–0 cell after the super-resolution image restoration. (a) Before the treatment of EGF. (b) 10 minutes after the treatment of 50 ng/ml EGF. The white arrows indicate the countable filopodia.

Fig. 7.
Fig. 7.

Time-lapse images of two filopodia of a CL1–0 cell before and after the treatment of EGF. Region (a) shows the elongation and shrinkage of a filopodium before the treatment. Region (b) is the case after the treatment. The numbers under each panel represent the image-capture time in min:sec. The filopodia also vibrate as they elongate and shrink.

Metrics