Abstract

We report a novel optical-tweezers-based method to study the membrane motion at the leading edge of biological cells with nanometer spatial and microsecond temporal resolution. A diffraction-limited laser spot was positioned at the leading edge of a cell, and the forward scattered light was imaged on a quadrant photodiode that served as a position sensitive device. The universality of this technique is demonstrated with different cell types. We investigated the membrane motion at the leading edge of red blood cells in detail and showed that this technique can achieve simultaneous manipulation and detection of cellular edge dynamics with unprecedented precision.

© 2007 Optical Society of America

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    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]

2006

J. Gore, Z. Bryant, M. Nollmann, M. U. Le, N. R. Cozzarelli, and C. Bustamante, Nature 442, 836 (2006).
[CrossRef] [PubMed]

S. Suresh, J. Mater. Res. 21, 1871 (2006).
[CrossRef]

2005

S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, Acta Biomater. 1, 15 (2005).
[CrossRef]

2004

K. C. Neuman and S. M. Block, Rev. Sci. Instrum. 75, 2787 (2004).
[CrossRef]

2003

C. Bustamante, Z. Bryant, and S. B. Smith, Nature 421, 423 (2003).
[CrossRef] [PubMed]

C. Humpert and M. Baumann, Mol. Membr. Biol. 20, 155 (2003).
[CrossRef] [PubMed]

F. Takahashi, Y. Higashino, and H. Miyata, Biophys. J. 84, 2664 (2003).
[CrossRef] [PubMed]

1999

A. Bitler, A. Barbul, and R. Korenstein, J. Microsc. 193, 171 (1999).
[CrossRef] [PubMed]

C. Veigel, L. M. Coluccio, J. D. Jontes, J. C. Sparrow, R. A. Milligan, and J. E. Molloy, Nature 398, 530 (1999).
[CrossRef] [PubMed]

1995

H. Strey, M. Peterson, and E. Sackmann, Biophys. J. 69, 478 (1995).
[CrossRef] [PubMed]

1994

J. T. Finer, R. M. Simmons, and J. A. Spudich, Nature 368, 113 (1994).
[CrossRef] [PubMed]

1990

S. M. Block, L. S. Goldstein, and B. J. Schnapp, Nature 348, 348 (1990).
[CrossRef] [PubMed]

1987

A. Ashkin, J. M. Dziedzic, and T. Yamane, Nature 330, 769 (1987).
[CrossRef] [PubMed]

A. Ashkin and J. M. Dziedzic, Science 235, 1517 (1987).
[CrossRef] [PubMed]

1975

F. Brochard and J. F. Lennon, J. Phys. (Paris) 36, 1035 (1975).
[CrossRef]

Ashkin, A.

A. Ashkin and J. M. Dziedzic, Science 235, 1517 (1987).
[CrossRef] [PubMed]

A. Ashkin, J. M. Dziedzic, and T. Yamane, Nature 330, 769 (1987).
[CrossRef] [PubMed]

Barbul, A.

A. Bitler, A. Barbul, and R. Korenstein, J. Microsc. 193, 171 (1999).
[CrossRef] [PubMed]

Baumann, M.

C. Humpert and M. Baumann, Mol. Membr. Biol. 20, 155 (2003).
[CrossRef] [PubMed]

Beil, M.

S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, Acta Biomater. 1, 15 (2005).
[CrossRef]

Bitler, A.

A. Bitler, A. Barbul, and R. Korenstein, J. Microsc. 193, 171 (1999).
[CrossRef] [PubMed]

Block, S. M.

K. C. Neuman and S. M. Block, Rev. Sci. Instrum. 75, 2787 (2004).
[CrossRef]

S. M. Block, L. S. Goldstein, and B. J. Schnapp, Nature 348, 348 (1990).
[CrossRef] [PubMed]

Brochard, F.

F. Brochard and J. F. Lennon, J. Phys. (Paris) 36, 1035 (1975).
[CrossRef]

Bryant, Z.

J. Gore, Z. Bryant, M. Nollmann, M. U. Le, N. R. Cozzarelli, and C. Bustamante, Nature 442, 836 (2006).
[CrossRef] [PubMed]

C. Bustamante, Z. Bryant, and S. B. Smith, Nature 421, 423 (2003).
[CrossRef] [PubMed]

Bustamante, C.

J. Gore, Z. Bryant, M. Nollmann, M. U. Le, N. R. Cozzarelli, and C. Bustamante, Nature 442, 836 (2006).
[CrossRef] [PubMed]

C. Bustamante, Z. Bryant, and S. B. Smith, Nature 421, 423 (2003).
[CrossRef] [PubMed]

Coluccio, L. M.

C. Veigel, L. M. Coluccio, J. D. Jontes, J. C. Sparrow, R. A. Milligan, and J. E. Molloy, Nature 398, 530 (1999).
[CrossRef] [PubMed]

Cozzarelli, N. R.

J. Gore, Z. Bryant, M. Nollmann, M. U. Le, N. R. Cozzarelli, and C. Bustamante, Nature 442, 836 (2006).
[CrossRef] [PubMed]

Dao, M.

S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, Acta Biomater. 1, 15 (2005).
[CrossRef]

Dziedzic, J. M.

A. Ashkin, J. M. Dziedzic, and T. Yamane, Nature 330, 769 (1987).
[CrossRef] [PubMed]

A. Ashkin and J. M. Dziedzic, Science 235, 1517 (1987).
[CrossRef] [PubMed]

Finer, J. T.

J. T. Finer, R. M. Simmons, and J. A. Spudich, Nature 368, 113 (1994).
[CrossRef] [PubMed]

Goldstein, L. S.

S. M. Block, L. S. Goldstein, and B. J. Schnapp, Nature 348, 348 (1990).
[CrossRef] [PubMed]

Gore, J.

J. Gore, Z. Bryant, M. Nollmann, M. U. Le, N. R. Cozzarelli, and C. Bustamante, Nature 442, 836 (2006).
[CrossRef] [PubMed]

Higashino, Y.

F. Takahashi, Y. Higashino, and H. Miyata, Biophys. J. 84, 2664 (2003).
[CrossRef] [PubMed]

Humpert, C.

C. Humpert and M. Baumann, Mol. Membr. Biol. 20, 155 (2003).
[CrossRef] [PubMed]

Jontes, J. D.

C. Veigel, L. M. Coluccio, J. D. Jontes, J. C. Sparrow, R. A. Milligan, and J. E. Molloy, Nature 398, 530 (1999).
[CrossRef] [PubMed]

Korenstein, R.

A. Bitler, A. Barbul, and R. Korenstein, J. Microsc. 193, 171 (1999).
[CrossRef] [PubMed]

Le, M. U.

J. Gore, Z. Bryant, M. Nollmann, M. U. Le, N. R. Cozzarelli, and C. Bustamante, Nature 442, 836 (2006).
[CrossRef] [PubMed]

Lennon, J. F.

F. Brochard and J. F. Lennon, J. Phys. (Paris) 36, 1035 (1975).
[CrossRef]

Lim, C. T.

S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, Acta Biomater. 1, 15 (2005).
[CrossRef]

Micoulet, A.

S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, Acta Biomater. 1, 15 (2005).
[CrossRef]

Milligan, R. A.

C. Veigel, L. M. Coluccio, J. D. Jontes, J. C. Sparrow, R. A. Milligan, and J. E. Molloy, Nature 398, 530 (1999).
[CrossRef] [PubMed]

Mills, J. P.

S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, Acta Biomater. 1, 15 (2005).
[CrossRef]

Miyata, H.

F. Takahashi, Y. Higashino, and H. Miyata, Biophys. J. 84, 2664 (2003).
[CrossRef] [PubMed]

Molloy, J. E.

C. Veigel, L. M. Coluccio, J. D. Jontes, J. C. Sparrow, R. A. Milligan, and J. E. Molloy, Nature 398, 530 (1999).
[CrossRef] [PubMed]

Neuman, K. C.

K. C. Neuman and S. M. Block, Rev. Sci. Instrum. 75, 2787 (2004).
[CrossRef]

Nollmann, M.

J. Gore, Z. Bryant, M. Nollmann, M. U. Le, N. R. Cozzarelli, and C. Bustamante, Nature 442, 836 (2006).
[CrossRef] [PubMed]

Peterson, M.

H. Strey, M. Peterson, and E. Sackmann, Biophys. J. 69, 478 (1995).
[CrossRef] [PubMed]

Sackmann, E.

H. Strey, M. Peterson, and E. Sackmann, Biophys. J. 69, 478 (1995).
[CrossRef] [PubMed]

Schnapp, B. J.

S. M. Block, L. S. Goldstein, and B. J. Schnapp, Nature 348, 348 (1990).
[CrossRef] [PubMed]

Seufferlein, T.

S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, Acta Biomater. 1, 15 (2005).
[CrossRef]

Simmons, R. M.

J. T. Finer, R. M. Simmons, and J. A. Spudich, Nature 368, 113 (1994).
[CrossRef] [PubMed]

Smith, S. B.

C. Bustamante, Z. Bryant, and S. B. Smith, Nature 421, 423 (2003).
[CrossRef] [PubMed]

Sparrow, J. C.

C. Veigel, L. M. Coluccio, J. D. Jontes, J. C. Sparrow, R. A. Milligan, and J. E. Molloy, Nature 398, 530 (1999).
[CrossRef] [PubMed]

Spatz, J.

S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, Acta Biomater. 1, 15 (2005).
[CrossRef]

Spudich, J. A.

J. T. Finer, R. M. Simmons, and J. A. Spudich, Nature 368, 113 (1994).
[CrossRef] [PubMed]

Strey, H.

H. Strey, M. Peterson, and E. Sackmann, Biophys. J. 69, 478 (1995).
[CrossRef] [PubMed]

Suresh, S.

S. Suresh, J. Mater. Res. 21, 1871 (2006).
[CrossRef]

S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, Acta Biomater. 1, 15 (2005).
[CrossRef]

Takahashi, F.

F. Takahashi, Y. Higashino, and H. Miyata, Biophys. J. 84, 2664 (2003).
[CrossRef] [PubMed]

Veigel, C.

C. Veigel, L. M. Coluccio, J. D. Jontes, J. C. Sparrow, R. A. Milligan, and J. E. Molloy, Nature 398, 530 (1999).
[CrossRef] [PubMed]

Yamane, T.

A. Ashkin, J. M. Dziedzic, and T. Yamane, Nature 330, 769 (1987).
[CrossRef] [PubMed]

Acta Biomater.

S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, Acta Biomater. 1, 15 (2005).
[CrossRef]

Biophys. J.

H. Strey, M. Peterson, and E. Sackmann, Biophys. J. 69, 478 (1995).
[CrossRef] [PubMed]

F. Takahashi, Y. Higashino, and H. Miyata, Biophys. J. 84, 2664 (2003).
[CrossRef] [PubMed]

J. Mater. Res.

S. Suresh, J. Mater. Res. 21, 1871 (2006).
[CrossRef]

J. Microsc.

A. Bitler, A. Barbul, and R. Korenstein, J. Microsc. 193, 171 (1999).
[CrossRef] [PubMed]

J. Phys. (Paris)

F. Brochard and J. F. Lennon, J. Phys. (Paris) 36, 1035 (1975).
[CrossRef]

Mol. Membr. Biol.

C. Humpert and M. Baumann, Mol. Membr. Biol. 20, 155 (2003).
[CrossRef] [PubMed]

Nature

A. Ashkin, J. M. Dziedzic, and T. Yamane, Nature 330, 769 (1987).
[CrossRef] [PubMed]

J. Gore, Z. Bryant, M. Nollmann, M. U. Le, N. R. Cozzarelli, and C. Bustamante, Nature 442, 836 (2006).
[CrossRef] [PubMed]

C. Bustamante, Z. Bryant, and S. B. Smith, Nature 421, 423 (2003).
[CrossRef] [PubMed]

J. T. Finer, R. M. Simmons, and J. A. Spudich, Nature 368, 113 (1994).
[CrossRef] [PubMed]

C. Veigel, L. M. Coluccio, J. D. Jontes, J. C. Sparrow, R. A. Milligan, and J. E. Molloy, Nature 398, 530 (1999).
[CrossRef] [PubMed]

S. M. Block, L. S. Goldstein, and B. J. Schnapp, Nature 348, 348 (1990).
[CrossRef] [PubMed]

Rev. Sci. Instrum.

K. C. Neuman and S. M. Block, Rev. Sci. Instrum. 75, 2787 (2004).
[CrossRef]

Science

A. Ashkin and J. M. Dziedzic, Science 235, 1517 (1987).
[CrossRef] [PubMed]

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Figures (3)

Fig. 1
Fig. 1

(a) Experimental setup using back focal plane imaging of the objective on a QPD. (b) Brightfield image of a red blood cell and the laser spot. The black line at the cell edge shows the region that is typically chosen for a laser scan to determine the cell edge.

Fig. 2
Fig. 2

QPD calibration curves. (a) 2.1 μ m laser raster scan of 21 nm steps over the edge of an RBC. Data was smoothed over five adjacent points and then linearly fitted. (b) 42 nm steps laser scan over the leading edge of a fish keratocyte. Data were smoothed over three adjacent points. Typically the error of the linear fit was below 8%.

Fig. 3
Fig. 3

(a) Cell edge fluctuation behavior of an RBC over the recording time of 60 s . The mean position of the entire recording was subtracted. (b) Histogram of the fluctuations shown in (a). (c) Bilogarithmic plot of the frequency spectrum of the cell edge fluctuations. Good agreement between experiment and theory which predicts a slope of 5 6 . (d) Normalized fluctuation histogram for three different laser powers impinging on the cell edge. The laser-induced force acting on the cell edge decreased the cell edge fluctuations.

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