Liposome adhesion generates traction stress

Journal name:
Nature Physics
Year published:
Published online


Mechanical forces generated by cells modulate global shape changes required for essential life processes, such as polarization, division and spreading. Although the contribution of the cytoskeleton to cellular force generation is widely recognized, the role of the membrane is considered to be restricted to passively transmitting forces. Therefore, the mechanisms by which the membrane can directly contribute to cell tension are overlooked and poorly understood. To address this, we directly measure the stresses generated during liposome adhesion. We find that liposome spreading generates large traction stresses on compliant substrates. These stresses can be understood as the equilibration of internal, hydrostatic pressures generated by the enhanced membrane tension built up during adhesion. These results underscore the role of membranes in the generation of mechanical stresses on cellular length scales and that the modulation of hydrostatic pressure due to membrane tension and adhesion can be channelled to perform mechanical work on the environment.

At a glance


  1. The dynamics of liposome spreading depends on substrate stiffness.
    Figure 1: The dynamics of liposome spreading depends on substrate stiffness.

    a, Diagram of liposome approach (P0), adhesion (P1) and spreading (P2/P3) on adhesive and stiff substrates that raises their membrane tension (τ, red arrows) and induces their rupture (P4). The width of the arrows reflects the magnitude of the tension. b, Liposome visualized by fluorescently labelled lipid (TR-DHPE) at the contact zone during the dynamics of spreading outlined in a. c, Normalized spread area over time for liposomes on 165kPa (filled symbols) and 1.3kPa (open symbols) poly-L-lysine-coated PAA gels. Each coloured line represents a different liposome sample. d, Spread area of liposomes on gels with modulus E=1.3kPa (same as c) over longer times. e, TR-DHPE at the contact zone immediately before rupture, at 65s (green) and during rupture at 70s (red). White dotted line indicates zoomed-in region below.

  2. Liposome adhesion deforms soft substrates.
    Figure 2: Liposome adhesion deforms soft substrates.

    a, Fluorescence images (TR-DHPE) of a liposome during contraction on a 1.8kPa gel, 315, 435 and 570s after the start of P3. b, Fluorescence images of 40nm beads beneath the liposome in a. The circle indicates the position of the liposome in a. c, Substrate deformation measured by displacement of embedded beads shown in a (×10 magnified). d, Averaged radial bead displacement (black) and averaged z-bead displacement (red) as a function of distance from the centre of the liposome, r. Error bars indicate the standard deviation. ez-displacement (uz) of the centre of the liposome over time. Inset: diagram of the volume of the liposome that lies below the initial surface (red dotted line). f, Elastic strain energy (black) and liposome contact area (red) over time corresponding to the deformations of the gel in c. Inset: elastic strain energy plotted against contact area. g, Schematic of the radial displacement (black) and the vertical displacement (red) with the net displacement vectors (green) of a liposome at its peak contracted state.

  3. Substrate traction stress varies with liposome size.
    Figure 3: Substrate traction stress varies with liposome size.

    a, Fluorescence images of a liposome spreading on a 1.3kPa PAA gel at times after the start of P0. b, Calculated in-plane traction stress induced by the spreading of liposomes. c, Mean in-plane traction stress (red) and mean traction strain (black) for liposomes less than 17μm in radius as a function of substrate stiffness, E. The traction stresses are measured for PAA stiffness, E=1.3, 1.8, 4.2 and 8.4kPa. Error bars indicate the standard deviation. The lines are intended to guide the eye. d, Mean in-plane traction strain as a function of the radius of the contact area between the liposome and substrate (E=8.4kPa).

  4. Substrate contraction induces compression of the membrane and budding of the bilayer at the contact zone.
    Figure 4: Substrate contraction induces compression of the membrane and budding of the bilayer at the contact zone.

    a, ‘Budding’ of the membrane during the compression of the bilayer within the contact zone on a 1.8kPa PAA gel during early P3 visualized by TR-DHPE fluorescence. The red line indicates the region over which the area is measured. b, Projected 2D area of the membrane buds in a over time, where each colour is a different bud (top); traction stress for the liposome over time (bottom). c,d, Confocal reconstruction of the bottom half (c) and top half (d) of an adherent liposome with ‘budding’ domains (TR-DHPE). Adjacent to each is the computed surface of the liposome showing a roughened surface. Red arrows point to membrane buds at the contact line. e, Image of a 3D projection of the bottom half of an adherent liposome showing buds emerging from the contact line. The red dotted line focuses on a bud that deflates in f. f, Bud deflates over time. Red line outlines bud. Images in a,e,f are inverted contrast.

  5. Minimization of energy drives substrate contraction.
    Figure 5: Minimization of energy drives substrate contraction.

    Diagram of substrate contraction. The liposome minimizes its energy by deforming the substrate to increase the charge density (blue) at the cost of the elastic strain energy. The increased membrane tension due to adhesion elevates the Laplace pressure (red) and indents the substrate. The thickness of the arrows represents the magnitude of the hydrostatic pressure.


  1. Boucrot, E. & Kirchhausen, T. Endosomal recycling controls plasma membrane area during mitosis. Proc. Natl Acad. Sci. USA 104, 79397944 (2007).
  2. Raucher, D. & Sheetz, M. P. Membrane expansion increases endocytosis rate during mitosis. J. Cell Biol. 144, 497506 (1999).
  3. Houk, A. R. et al. Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration. Cell 148, 175188 (2012).
  4. Gauthier, N. C., Fardin, M. A., Roca-Cusachs, P. & Sheetz, M. P. Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading. Proc. Natl Acad. Sci. USA 108, 1446714472 (2011).
  5. Yeung, T. et al. Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motil. Cytoskel. 60, 2434 (2005).
  6. Schwarz, U. S. & Gardel, M. L. United we stand: Integrating the actin cytoskeleton and cell-matrix adhesions in cellular mechanotransduction. J. Cell Sci. 125, 30513060 (2012).
  7. Batchelder, E. L. et al. Membrane tension regulates motility by controlling lamellipodium organization. Proc. Natl Acad. Sci. USA 108, 1142911434 (2011).
  8. Lipowsky, R. & Seifert, U. Adhesion of membranes—a theoretical perspective. Langmuir 7, 18671873 (1991).
  9. Lipowsky, R. & Seifert, U. Adhesion of vesicles and membranes. Mol. Cryst. Liq. Cryst. 202, 1725 (1991).
  10. Seifert, U. & Lipowsky, R. Adhesion of vesicles. Phys. Rev. A 42, 47684771 (1990).
  11. Albersdorfer, A., Feder, T. & Sackmann, E. Adhesion-induced domain formation by interplay of long-range repulsion and short-range attraction force: A model membrane study. Biophys. J. 73, 245257 (1997).
  12. Nardi, J., Bruinsma, R. & Sackmann, E. Adhesion-induced reorganization of charged fluid membranes. Phys. Rev. E 58, 63406354 (1998).
  13. Murrell, M. et al. Spreading dynamics of biomimetic actin cortices. Biophys. J. 100, 14001409 (2011).
  14. Bernard, A. L., Guedeau-Boudeville, M. A., Jullien, L. & di Meglio, J. M. Strong adhesion of giant vesicles on surfaces: Dynamics and permeability. Langmuir 16, 68096820 (2000).
  15. Brochard-Wyart, F. & de Gennes, P. G. Adhesion induced by mobile binders: Dynamics. Proc. Natl Acad. Sci. USA 99, 78547859 (2002).
  16. Cuvelier, D. & Nassoy, P. Hidden dynamics of vesicle adhesion induced by specific stickers. Phys. Rev. Lett. 93, 228101 (2004).
  17. Limozin, L. & Sengupta, K. Modulation of vesicle adhesion and spreading kinetics by hyaluronan cushions. Biophys. J. 93, 33003313 (2007).
  18. Olbrich, K., Rawicz, W., Needham, D. & Evans, E. Water permeability and mechanical strength of polyunsaturated lipid bilayers. Biophys. J. 79, 321327 (2000).
  19. Sandre, O., Moreaux, L. & Brochard-Wyart, F. Dynamics of transient pores in stretched vesicles. Proc. Natl Acad. Sci. USA 96, 1059110596 (1999).
  20. Evans, E., Heinrich, V., Ludwig, F. & Rawicz, W. Dynamic tension spectroscopy and strength of biomembranes. Biophys. J. 85, 23422350 (2003).
  21. Sabass, B., Gardel, M. L., Waterman, C. M. & Schwarz, U. S. High resolution traction force microscopy based on experimental and computational advances. Biophys. J. 94, 207220 (2008).
  22. Hategan, A., Law, R., Kahn, S. & Discher, D. E. Adhesively-tensed cell membranes: Lysis kinetics and atomic force microscopy probing. Biophys. J. 85, 27462759 (2003).
  23. Style, R. W. & Dufresne, E. R. Static wetting on deformable substrates, from liquids to soft solids. Soft Matter 8, 71777184 (2012).
  24. Staykova, M., Holmes, D. P., Read, C. & Stone, H. A. Mechanics of surface area regulation in cells examined with confined lipid membranes. Proc. Natl Acad. Sci. USA 108, 90849088 (2011).
  25. Christian, D. A. et al. Spotted vesicles, striped micelles and Janus assemblies induced by ligand binding. Nature Mater. 8, 843849 (2009).
  26. Hategan, A., Sengupta, K., Kahn, S., Sackmann, E. & Discher, D.E. Topographical pattern dynamics in passive adhesion of cell membranes. Biophys. J. 87, 35473560 (2004).
  27. Gordon, V. D., Deserno, M., Andrew, C. M. J., Egelhaaf, S. U. & Poon, W. C. K. Adhesion promotes phase separation in mixed-lipid membranes. Europhys. Lett. 84, 48003 (2008).
  28. Rouhiparkouhi, T., Weikl, T. R., Discher, D. E. & Lipowsky, R. Adhesion-induced phase behavior of two-component membranes and vesicles. Int. J. Mol. Sci. 14, 22032229 (2013).
  29. Norman, L., Sengupta, K. & Aranda-Espinoza, H. Blebbing dynamics during endothelial cell spreading. Eur. J. Cell Biol. 90, 3748 (2011).
  30. Norman, L. L., Brugues, J., Sengupta, K., Sens, P. & Aranda-Espinoza, H. Cell blebbing and membrane area homeostasis in spreading and retracting cells. Biophys. J. 99, 17261733 (2010).
  31. Myat, M. M., Anderson, S., Allen, L. A. & Aderem, A. MARCKS regulates membrane ruffling and cell spreading. Curr. Biol. 7, 611614 (1997).
  32. Dai, J. W., Sheetz, M. P., Wan, X. D. & Morris, C. E. Membrane tension in swelling and shrinking molluscan neurons. J. Neurosci. 18, 66816692 (1998).
  33. Delanoe-Ayari, H., Rieu, J. P. & Sano, M. 4D traction force microscopy reveals asymmetric cortical forces in migrating Dictyostelium cells. Phys. Rev. Lett. 105, 248103 (2010).
  34. Maskarinec, S. A., Franck, C., Tirrell, D. A. & Ravichandran, G. Quantifying cellular traction forces in three dimensions. Proc. Natl Acad. Sci. USA 106, 2210822113 (2009).
  35. Wang, N., Ostuni, E., Whitesides, G. M. & Ingber, D. E. Micropatterning tractional forces in living cells. Cell Motil. Cytoskeleton 52, 97106 (2002).
  36. Yip, A. K. et al. Cellular response to substrate rigidity is governed by either stress or strain. Biophys. J. 104, 1929 (2013).
  37. Oakes, P. W., Beckham, Y., Stricker, J. & Gardel, M. L. Tension is required but not sufficient for focal adhesion maturation without a stress fiber template. J. Cell Biol. 196, 363374 (2012).
  38. Califano, J. P. & Reinhart-King, C. A. Substrate stiffness and cell area predict cellular traction stresses in single cells and cells in contact. Cell. Mol. Bioeng. 3, 6875 (2010).

Download references

Author information

  1. These authors contributed equally to this work

    • Pierre Nassoy,
    • Cécile Sykes &
    • Margaret L. Gardel


  1. Institute for Biophysical Dynamics, James Franck Institute, University of Chicago, Chicago, Illinois I60637, USA

    • Michael P. Murrell &
    • Margaret L. Gardel
  2. Institut Curie, Centre de Recherche, Laboratoire Physico-Chimie, UMR168, Paris F-75248, France

    • Michael P. Murrell,
    • Jean-François Joanny,
    • Pierre Nassoy &
    • Cécile Sykes
  3. Centre National de la Recherche Scientifique, UMR168, Paris F-75248, France

    • Michael P. Murrell,
    • Jean-François Joanny,
    • Pierre Nassoy &
    • Cécile Sykes
  4. Université Paris 6, Paris F-75248, France

    • Michael P. Murrell,
    • Jean-François Joanny,
    • Pierre Nassoy &
    • Cécile Sykes
  5. Laboratoire Jean Perrin, CNRS FRE 3231, and Laboratoire de Physique Théorique de la Matière Condensée, CNRS UMR 7600, Université Pierre et Marie Curie, 4 place Jussieu, Paris F-75005, France

    • Raphaël Voituriez
  6. Institut d’Optique, LP2N, UMR 5298, Talence F-33405, France

    • Pierre Nassoy
  7. The Department of Physics, University of Chicago, Chicago, Illinois I60637, USA

    • Margaret L. Gardel


M.P.M. performed experiments. M.L.G. developed analytical tools. R.V., J-F.J., P.N. and C.S. contributed theory and calculations. M.P.M., R.V., J-F.J., P.N., C.S. and M.L.G. wrote the paper.

Competing financial interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to:

Author details

Supplementary information

PDF files

  1. Supplementary Information (1677KB)

    Supplementary Information


  1. Supplementary Movie (2537KB)

    Supplementary Movie 1

  2. Supplementary Movie (3493KB)

    Supplementary Movie 2

  3. Supplementary Movie (1520KB)

    Supplementary Movie 3

  4. Supplementary Movie (5179KB)

    Supplementary Movie 4

  5. Supplementary Movie (2169KB)

    Supplementary Movie 5

  6. Supplementary Movie (1113KB)

    Supplementary Movie 6

  7. Supplementary Movie (280KB)

    Supplementary Movie 7

  8. Supplementary Movie (1885KB)

    Supplementary Movie 8

  9. Supplementary Movie (2993KB)

    Supplementary Movie 9

Additional data