Jean Baudry

Microscopic artificial swimmers

Microorganisms such as bacteria and many eukaryotic cells propel themselves with hair-like structures known as flagella, which can exhibit a variety of structures and movement patterns. For example, bacterial flagella are helically shaped and driven at their bases by a reversible rotary engine, which rotates the attached flagellum to give a motion similar to that of a corkscrew. In contrast, eukaryotic cells use flagella that resemble elastic rods and exhibit a beating motion: internally generated stresses give rise to a series of bends that propagate towards the tip. In contrast to this variety of swimming strategies encountered in nature, a controlled swimming motion of artificial micrometre-sized structures has not yet been realized. Here we show that a linear chain of colloidal magnetic particles linked by DNA and attached to a red blood cell can act as a flexible artificial flagellum. The filament aligns with an external uniform magnetic field and is readily actuated by oscillating a transverse field. We find that the actuation induces a beating pattern that propels the structure, and that the external fields can be adjusted to control the velocity and the direction of motion.

Chiral colloidal clusters

Chirality is an important element of biology, chemistry and physics. Once symmetry is broken and a handedness is established, biochemical pathways are set. In DNA, the double helix arises from the existence of two competing length scales, one set by the distance between monomers in the sugar backbone, and the other set by the stacking of the base pairs. Here we use a colloidal system to explore a simple forcing route to chiral structures. To do so we have designed magnetic colloids that, depending on both their shape and induced magnetization, self-assemble with controlled helicity. We model the two length scales with asymmetric colloidal dumbbells linked by a magnetic belt at their waist. In the presence of a magnetic field the belts assemble into a chain and the steric constraints imposed by the asymmetric spheres force the chain to coil. We show that if the size ratio between the spheres is large enough, a single helicity is adopted, right or left. The realization of chiral colloidal clusters opens up a new link between colloidal science and chemistry. These colloidal clusters may also find use as mesopolymers, as optical and light-activated structures, and as models for enantiomeric separation.

Combining Mixture Components for Clustering

Model-based clustering consists of fitting a mixture model to data and identifying each cluster with one of its components. Multivariate normal distributions are typically used. The number of clusters is usually determined from the data, often using BIC. In practice, however, individual clusters can be poorly fitted by Gaussian distributions, and in that case model-based clustering tends to represent one non-Gaussian cluster by a mixture of two or more Gaussian distributions. If the number of mixture components is interpreted as the number of clusters, this can lead to overestimation of the number of clusters. This is because BIC selects the number of mixture components needed to provide a good approximation to the density, rather than the number of clusters as such. We propose first selecting the total number of Gaussian mixture components, K, using BIC and then combining them hierarchically according to an entropy criterion. This yields a unique soft clustering for each number of clusters less than or equal to K. These clusterings can be compared on substantive grounds, and we also describe an automatic way of selecting the number of clusters via a piecewise linear regression fit to the rescaled entropy plot. We illustrate the method with simulated data and a flow cytometry dataset. Supplemental materials are available on the journal web site and described at the end of the article.

Acceleration of the recognition rate between grafted ligands and receptors with magnetic forces

When ligands and receptors are both attached on surfaces, because of the restriction of configurational freedom, their recognition kinetics may be substantially reduced as compared with freely diffusing species. In nature, this reduction may influence the efficiency of the capture and adhesion of circulating cells. Here we show that similar consequences are observed for colloids grafted with biomolecules that are used as probes for diagnostics. We exploit Brownian magnetic colloids that self-assemble into linear chains to show also that the resulting one-dimensional confinement considerably accelerates the recognition rate between grafted receptors and their ligands. We propose that because confinement significantly augments the colliding frequency, it also causes a large increase in the attempt frequency of the recognition. This work gives the basis of a rapid, homogeneous, and highly sensitive bioanalysis method.

On the dynamics of magnetically driven elastic filaments

Following a novel realization of low-Reynolds-number swimming (Dreyfus et al. , Nature , vol. 436, 2005, p. 862), in which self-assembled filaments of paramagnetic micron-sized beads are tethered to red blood cells and then induced to swim under crossed uniform and oscillating magnetic fields, the dynamics of magnetoelastic filaments is studied. The filament is modelled as a slender elastica driven by a magnetic body torque. The model is applied to experiments of Goubault et al. ( Phys. Rev. Lett. , vol. 91, 2003, art. 260802) to predict the lifetimes of metastable static filament conformations that are known to form under uniform fields. A second experimental swimming scenario, complementary to that of Dreyfus et al. (2005), is described: filaments are capable of swimming even if not tethered to red blood cells. Yet, if both ends of the filament are left free and the material and magnetic parameters are uniform along its length then application of an oscillating transverse field can only generate homogeneous torques, and net translation is prohibited by symmetry. It is shown that fore–aft symmetry is broken when variation of the bending stiffness along the filament is accounted for by including elastic defects, which produces results consistent with the swimming phenomenology.

Monitoring single-cell bioenergetics via the coarsening of emulsion droplets

Microorganisms are widely used to generate valuable products, and their efficiency is a major industrial focus. Bioreactors are typically composed of billions of cells, and available measurements only reflect the overall performance of the population. However, cells do not equally contribute, and process optimization would therefore benefit from monitoring this intrapopulation diversity. Such monitoring has so far remained difficult because of the inability to probe concentration changes at the single-cell level. Here, we unlock this limitation by taking advantage of the osmotically driven water flux between a droplet containing a living cell toward surrounding empty droplets, within a concentrated inverse emulsion. With proper formulation, excreted products are far more soluble within the continuous hydrophobic phase compared to initial nutrients (carbohydrates and salts). Fast diffusion of products induces an osmotic mismatch, which further relaxes due to slower diffusion of water through hydrophobic interfaces. By measuring droplet volume variations, we can deduce the metabolic activity down to isolated single cells. As a proof of concept, we present the first direct measurement of the maintenance energy of individual yeast cells. This method does not require any added probes and can in principle apply to any osmotically sensitive bioactivity, opening new routes for screening, and sorting large libraries of microorganisms and biomolecules.

Force-velocity measurements of a few growing actin filaments.

The authors propose a new mechanism for actin-based force generation based on results using chains of actin-grafted magnetic colloids.

A Millifluidic Study of Cell-to-Cell Heterogeneity in Growth-Rate and Cell-Division Capability in Populations of Isogenic Cells of Chlamydomonas reinhardtii

To address possible cell-to-cell heterogeneity in growth dynamics of isogenic cell populations of Chlamydomonas reinhardtii, we developed a millifluidic drop-based device that not only allows the analysis of populations grown from single cells over periods of a week, but is also able to sort and collect drops of interest, containing viable and healthy cells, which can be used for further experimentation. In this study, we used isogenic algal cells that were first synchronized in mixotrophic growth conditions. We show that these synchronized cells, when placed in droplets and kept in mixotrophic growth conditions, exhibit mostly homogeneous growth statistics, but with two distinct subpopulations: a major population with a short doubling-time (fast-growers) and a significant subpopulation of slowly dividing cells (slow-growers). These observations suggest that algal cells from an isogenic population may be present in either of two states, a state of restricted division and a state of active division. When isogenic cells were allowed to propagate for about 1000 generations on solid agar plates, they displayed an increased heterogeneity in their growth dynamics. Although we could still identify the original populations of slow- and fast-growers, drops inoculated with a single progenitor cell now displayed a wider diversity of doubling-times. Moreover, populations dividing with the same growth-rate often reached different cell numbers in stationary phase, suggesting that the progenitor cells differed in the number of cell divisions they could undertake. We discuss possible explanations for these cell-to-cell heterogeneities in growth dynamics, such as mutations, differential aging or stochastic variations in metabolites and macromolecules yielding molecular switches, in the light of single-cell heterogeneities that have been reported among isogenic populations of other eu- and prokaryotes.

Specific wetting probed with biomimetic emulsion droplets

We have produced emulsion droplets of controlled size and composition coated by ligands, and studied the adhesion of these drops on a solid substrate coated by receptors and polymers. Using transmission, RICM and fluorescence microscopy we assess the size, contact angle and ligand density for each drop. We first show that non-specific interactions significantly enhance the proteins density within the adhesive patch. Then we show that binding within the patch is partially inhibited in good agreement with the hypothesis of an absence of translational diffusion. We confirm that the density of specific bonds sets the adhesive energy and therefore the final contact angle, and finally show that specific binding in our system is always associated with the existence of a positive line tension, which linearly increases with the density of receptors. These experiments describe a new scenario for specific wetting which raises the importance of the coupling between non-specific interactions and specific binding.

Measuring colloidal forces with the magnetic chaining technique

In 1994 Leal Calderon et al. (Phys. Rev. Lett. 72, 2959 (1994)) introduced the magnetic chaining technique to directly probe the force-distance profile between colloidal particles. In this paper, we revisit this approach in two ways. First, we describe a new experimental design which allows us to utilize sample volumes as low as a few microliters, involving femtomoles of surface active macromolecules. Secondly, we extensively describe the characterization and preparation of the magnetic colloids, and we give a quantitative evaluation of performance and resolution of the technique in terms of force and interparticle separation.