Elie Wandersman

Professor, Physics Department, Sorbonne Université

Head of the Master 2 programme Soft Matter Physics and Engineering

Head of the Master 1 bidisciplinary programme Physique et Mécanique

I am a soft matter physicist working at the interface with biology. I build simplified, well-controlled model systems to understand how mechanics shapes living matter. My current research focuses on active biomimetic tissues and on the rheology of the cytoplasm during early embryonic development. I previously worked on the physics of touch, using biomimetic mechanoreceptors and sensory organs, and on molecular transport in artificial tissues.

Current research

Active biomimetic tissues

Living tissues are active materials. Cells consume ATP to generate forces, and cell–cell adhesion transmits these forces across the tissue. This leads to large-scale deformations and collective rearrangements, as seen during morphogenesis. Artificial cells containing cytoskeletal motors are known to deform strongly. However, no active multicellular model yet exists to study quantitatively how internal activity controls collective dynamics, plasticity and rheology.

We build such active artificial tissues from networks of Droplet Interface Bilayers (DIBs). In these networks, aqueous droplets bathed in a lipid/oil mixture adhere to each other through spontaneously formed lipid bilayers. Each droplet encapsulates an active motor–filament system: microtubule/kinesin, actin/myosin, or hybrids. We tune three parameters, the internal activity, the filament composition and the adhesion between droplets, and study how each governs the emergence of collective behavior.

We can already encapsulate active systems in droplets and image the internal active flows by fluorescence microscopy. We assemble reproducible 2D tissues of several tens of droplets that remain stable for hours, which lets us track both individual and collective dynamics. At high ATP concentration, microtubule-based tissues show strong droplet deformations and T1 neighbor exchanges, a hallmark of emerging collective plasticity. We are now systematically exploring how activity, deformation and rearrangements relate, and under which conditions these tissues behave as active solids or active fluids.

In collaboration with Jean-Christophe Galas (LJP) and Alexandra Colin (CytoMorphoLab, CEA/CNRS/Univ. Grenoble Alpes).

Cytoplasm rheology in early embryonic development

The cytoplasm is a dense, heterogeneous medium where most biochemical reactions and intracellular reorganizations take place. It contains three kinds of components:

• nanometric macromolecules (proteins, RNA, ribosomes);
• micrometric vesicles and endomembrane structures;
• active cytoskeletal networks.

Together, these components make the cytoplasm viscoelastic. Its viscosity is roughly 100 to 1000 times that of water, and its stiffness, about 1 to 100 Pa, is comparable to that of a soft gel. The response also depends on force amplitude, loading rate and probe size. At the molecular scale, the cytoplasm is known to affect diffusion, reaction rates and phase separation. How it controls the motion of larger, micron-sized objects, which matter for cell division and morphogenesis, remains largely unexplored.

In collaboration with Nicolas Minc’s team (Institut Jacques Monod, CNRS/Université Paris Cité), we address this question using sea urchin eggs and embryos, following two lines of work.

What sets the mechanics of the cytoplasm? We hypothesize that, at the scale of large organelles, cytoplasm mechanics is dominated by the crowding of endomembrane vesicles, sheets and tubules, which behave as a dense heterogeneous suspension. Three approaches test this idea:

• Imaging. 3D electron microscopy of unfertilized eggs reveals the spatial organization of endomembranes and yolk granules.
• In vivo measurements. Magnetic tweezers probe the rheology of living eggs under controlled perturbations: energy supply, macromolecular crowding, and endomembrane organization.
• Synthetic cells. We fractionate cytoplasmic extracts by centrifugation, encapsulate each fraction in ~100 µm water-in-oil droplets made with our “capillary trap” method, and measure their viscoelastic signatures with embedded magnetic particles. By recombining fractions in varying proportions, we aim to reconstitute the mechanical signature of the living cytoplasm.

How does cytoplasm mechanics change during development, and why does it matter? Preliminary results show that the cytoplasm stiffens progressively from the 1-cell to the 4-cell stage, and that this stiffening improves the mechanical stability of the mitotic spindle. We will map cytoplasm rheology from the 1-cell to the 32-cell stage. We will then perturb it in targeted ways, for example by stabilizing or depolymerizing the cytoskeleton or by adding viscogens such as trehalose, and assess the effects on cell division, cell-cycle duration and lineage specification.