Biology Inspired Physics at Mesoscales

Team Publications

Year of publication 2007

Jean Lehmann, Amy Reichel, Axel Buguin, Albert Libchaber (2007 Jun 9)

Efficiency of a self-aminoacylating ribozyme: effect of the length and base-composition of its 3′ extension.

RNA (New York, N.Y.) : 1191-7 Learn more
Summary

Variants of a previously described small self-aminoacylating ribozyme are tested in order to uncover the potentialities of a 3′ extension responsible for the esterification. The base-composition and the length of this specific part of the ribozyme are investigated. Very short extensions can still reach the active site, reflecting the small persistence length of RNA. The yield of aminoacylation is particularly high for ribozymes with extensions made up of a poly-U, for which a maximum of efficiency is observed for a total length of about 10 nucleotides. A simple model describing the behavior of this region of the ribozyme can account for the data.

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Alexandre Saez, Marion Ghibaudo, Axel Buguin, Pascal Silberzan, Benoît Ladoux (2007 May 10)

Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates.

Proceedings of the National Academy of Sciences of the United States of America : 8281-6 Learn more
Summary

The physical properties of the cellular environment are involved in regulating the formation and maintenance of tissues. In particular, substrate rigidity appears to be a key factor dictating cell response on culture surfaces. Here we study the behavior of epithelial cells cultured on microfabricated substrates engineered to exhibit an anisotropic stiffness. The substrate consists of a dense array of micropillars of oval cross-section, so that one direction is made stiffer than the other. We demonstrate how such an anisotropic rigidity can induce directional epithelial growth and guide cell migration along the direction of greatest rigidity. Regions of high tractional stress and large cellular deformations within the sheets of cells are concentrated at the edges, in particular at the two poles of the islands along their long axis, in correlation with the orientation of actin stress fibers and focal adhesions. By inducing scattering activity of epithelial cells, we show that isolated cells also migrate along the direction of greatest stiffness. Taken together, these findings show that the mechanical interactions of cells with their microenvironment can be tuned to engineer particular tissue properties.

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Year of publication 2006

Yunfei Cai, Nicolas Biais, Gregory Giannone, Monica Tanase, Guoying Jiang, Jake M Hofman, Chris H Wiggins, Pascal Silberzan, Axel Buguin, Benoit Ladoux, Michael P Sheetz (2006 Aug 22)

Nonmuscle myosin IIA-dependent force inhibits cell spreading and drives F-actin flow.

Biophysical journal : 3907-20 Learn more
Summary

Nonmuscle myosin IIA (NMM-IIA) is involved in the formation of focal adhesions and neurite retraction. However, the role of NMM-IIA in these functions remains largely unknown. Using RNA interference as a tool to decrease NMM-IIA expression, we have found that NMM-IIA is the major myosin involved in traction force generation and retrograde F-actin flow in mouse embryonic fibroblast cells. Quantitative analyses revealed that approximately 60% of traction force on fibronectin-coated surfaces is contributed by NMM-IIA and approximately 30% by NMM-IIB. The retrograde F-actin flow decreased dramatically in NMM-IIA-depleted cells, but seemed unaffected by NMM-IIB deletion. In addition, we found that depletion of NMM-IIA caused cells to spread at a higher rate and to a greater area on fibronectin substrates during the early spreading period, whereas deletion of NMM-IIB appeared to have no effect on spreading. The distribution of NMM-IIA was concentrated on the dorsal surface and approached the ventral surface in the periphery, whereas NMM-IIB was primarily concentrated around the nucleus and to a lesser extent at the ventral surface in cell periphery. Our results suggest that NMM-IIA is involved in generating a coherent cytoplasmic contractile force from one side of the cell to the other through the cross-linking and the contraction of dorsal actin filaments.

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Arthur Ganz, Mireille Lambert, Alexandre Saez, Pascal Silberzan, Axel Buguin, René Marc Mège, Benoît Ladoux (2006 Aug 10)

Traction forces exerted through N-cadherin contacts.

Biology of the cell / under the auspices of the European Cell Biology Organization : 721-30 Learn more
Summary

Mechanical forces play an important role in the organization, growth and function of living tissues. The ability of cells to transduce mechanical signals is governed by two types of microscale structures: focal adhesions, which link cells to the extracellular matrix, and adherens junctions, which link adjacent cells through cadherins. Although many studies have examined forces induced by focal adhesions, there is little known about the role of adherens junctions in force-regulation processes. The present study focuses on the determination of force transduction through cadherins at a single cell level.

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O du Roure, A Buguin, H Feracci, P Silberzan (2006 May 3)

Homophilic interactions between cadherin fragments at the single molecule level: an AFM study.

Langmuir : the ACS journal of surfaces and colloids : 4680-4 Learn more
Summary

We report measurements of the adhesion forces between single E-cadherin fragments anchored on solid surfaces. These fragments consist of the two outermost extracellular domains of the protein. The specificity of the measured rupture forces was demonstrated by Ca2+ exchange experiments. Two series of experiments were performed using two linkers of different rigidity and length. We find that the pull-off force is distributed with a maximum value independent of the linker and logarithmically dependent on the velocity of separation of the two surfaces. Our dynamical results are compatible with previous flow chamber experiments performed with the same fragments and can be compared from a different perspective with previously reported AFM experiments on the full-length extracellular domain of the VE-cadherin. Interestingly, using a rigid linker, we have been able for the first time to evidence the deformation of the cadherin molecule under mechanical stress, a piece of information not accessible with more classical grafting strategies.

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Axel Buguin, Min-Hui Li, Pascal Silberzan, Benoit Ladoux, Patrick Keller (2006 Jan 26)

Micro-actuators: when artificial muscles made of nematic liquid crystal elastomers meet soft lithography.

Journal of the American Chemical Society : 1088-9 Learn more
Summary

The production, via soft lithography, of micron-sized thermoresponsive pillars made of side-on nematic LCE leads to the formation of surface-responsive structures. The individual, monodisperse pillars, when cut out from the surface, behave as micro-actuators, showing contraction of around 35% at the nematic to isotropic phase transition.

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Year of publication 2005

Alexandre Saez, Axel Buguin, Pascal Silberzan, Benoît Ladoux (2005 Oct 7)

Is the mechanical activity of epithelial cells controlled by deformations or forces?

Biophysical journal : L52-4 Learn more
Summary

The traction forces developed by cells depend strongly on the substrate rigidity. In this letter, we characterize quantitatively this effect on MDCK epithelial cells by using a microfabricated force sensor consisting in a high-density array of soft pillars whose stiffness can be tailored by changing their height and radius to obtain a rigidity range from 2 nN/microm up to 130 nN/microm. We find that the forces exerted by the cells are proportional to the spring constant of the pillars meaning that, on average, the cells deform the pillars by the same amount whatever their rigidity. The relevant parameter may thus be a deformation rather than a force. These dynamic observations are correlated with the reinforcement of focal adhesions that increases with the substrate rigidity.

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Olivia du Roure, Alexandre Saez, Axel Buguin, Robert H Austin, Philippe Chavrier, Pascal Silberzan, Pascal Siberzan, Benoit Ladoux (2005 Feb 1)

Force mapping in epithelial cell migration.

Proceedings of the National Academy of Sciences of the United States of America : 2390-5 Learn more
Summary

We measure dynamic traction forces exerted by epithelial cells on a substrate. The force sensor is a high-density array of elastomeric microfabricated pillars that support the cells. Traction forces induced by cell migration are deduced from the measurement of the bending of these pillars and are correlated with actin localization by fluorescence microscopy. We use a multiple-particle tracking method to estimate the mechanical activity of cells in real time with a high-spatial resolution (down to 2 microm) imposed by the periodicity of the post array. For these experiments, we use differentiated Madin-Darby canine kidney (MDCK) epithelial cells. Our data provide definite information on mechanical forces exerted by a cellular assembly. The maximum intensity of the forces is localized on the edge of the epithelia. Hepatocyte growth factor promotes cell motility and induces strong scattering activity of MDCK cells. Thus, we compare forces generated by MDCK cells in subconfluent epithelia versus isolated cells after hepatocyte growth factor treatment. Maximal-traction stresses at the edge of a monolayer correspond to higher values than those measured for a single cell and may be due to a collective behavior.

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Year of publication 2004

X Noblin, A Buguin, F Brochard-Wyart (2004 Aug 17)

Vibrated sessile drops: transition between pinned and mobile contact line oscillations.

The European physical journal. E, Soft matter : 395-404 Learn more
Summary

We study the effects of vertical vibrations on non-wetting large water sessile drops flattened by gravity. The solid substrate is characterized by a finite contact angle hysteresis (10-15 degrees). By varying the frequency and the amplitude of the vertical displacement, we observe two types of oscillations. At low amplitude, the contact line remains pinned and the drop presents eigen modes at different resonance frequencies. At higher amplitude, the contact line moves: it remains circular but its radius oscillates at the excitation frequency. The transition between these two regimes arises when the variations of contact angle exceed the contact angle hysteresis. We interpret different features of these oscillations, such as the decrease of the resonance frequencies at larger vibration amplitudes. The hysteresis acts as “solid” friction on the contour oscillations, and gives rise to a stick-slip regime at intermediate amplitude.

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