Actomyosin clusters as active units shaping living matter.

Stress generation by the actin cytoskeleton shapes cells and tissues. Despite impressive progress in live imaging and quantitative physical descriptions of cytoskeletal network dynamics, the connection between processes at molecular scales and spatiotemporal patterns at the cellular scale is still unclear. Here, we review studies reporting actomyosin clusters of micrometre size and with lifetimes of several minutes in a large number of organisms, ranging from fission yeast to humans.

Tight junctions control lumen morphology via hydrostatic pressure and junctional tension.

Formation of fluid-filled lumina by epithelial tissues is essential for organ development. How cells control the hydraulic and cortical forces to control lumen morphology is not well understood. Here, we quantified the mechanical role of tight junctions in lumen formation using MDCK-II cysts.

UBAP2L ensures homeostasis of nuclear pore complexes at the intact nuclear envelope.

Assembly of macromolecular complexes at correct cellular sites is crucial for cell function. Nuclear pore complexes (NPCs) are large cylindrical assemblies with eightfold rotational symmetry, built through hierarchical binding of nucleoporins (Nups) forming distinct subcomplexes. Here, we uncover a role of ubiquitin-associated protein 2-like (UBAP2L) in the assembly and stability of properly organized and functional NPCs at the intact nuclear envelope (NE) in human cells.

Pulsations and flows in tissues as two collective dynamics with simple cellular rules.

Collective motions of epithelial cells are essential for morphogenesis. Tissues elongate, contract, flow, and oscillate, thus sculpting embryos. These tissue level dynamics are known, but the physical mechanisms at the cellular level are unclear.

3D single cell migration driven by temporal correlation between oscillating force dipoles.

Directional cell locomotion requires symmetry breaking between the front and rear of the cell. In some cells, symmetry breaking manifests itself in a directional flow of actin from the front to the rear of the cell. Many cells, especially in physiological 3D matrices, do not show such coherent actin dynamics and present seemingly competing protrusion/retraction dynamics at their front and back.

Computational approaches for simulating luminogenesis.

Lumens, liquid-filled cavities surrounded by polarized tissue cells, are elementary units involved in the morphogenesis of organs. Theoretical modeling and computations, which can integrate various factors involved in biophysics of morphogenesis of cell assembly and lumens, may play significant roles to elucidate the mechanisms in formation of such complex tissue with lumens. However, up to present, it has not been documented well what computational approaches or frameworks can be applied for this purpose and how we can choose the appropriate approach for each problem.

Interplay between cell height variations and planar pulsations in epithelial monolayers.

Biological tissues change their shapes through collective interactions of cells. This coordination sets length and time scales for dynamics where precision is essential, in particular during morphogenetic events. However, how these scales emerge remains unclear.

Epithelial colonies in vitro elongate through collective effects.

Epithelial tissues of the developing embryos elongate by different mechanisms, such as neighbor exchange, cell elongation, and oriented cell division. Since autonomous tissue self-organization is influenced by external cues such as morphogen gradients or neighboring tissues, it is difficult to distinguish intrinsic from directed tissue behavior. The mesoscopic processes leading to the different mechanisms remain elusive.

Ratchetaxis in Channels: Entry Point and Local Asymmetry Set Cell Directions in Confinement.

Cell motility is essential in a variety of biological phenomena ranging from early development to organ homeostasis and diseases. This phenomenon has mainly been studied and characterized on flat surfaces in vitro, whereas such conditions are rarely observed in vivo. Recently, cell motion in three-dimensional microfabricated channels was reported to be possible, and it was shown that confined cells push on walls.

Collective Dynamics of Focal Adhesions Regulate Direction of Cell Motion.

Directed cell motion is essential in physiological and pathological processes such as morphogenesis, wound healing, and cancer spreading. Chemotaxis has often been proposed as the driving mechanism, even though evidence of long-range gradients is often lacking in vivo. By patterning adhesive regions in space, we control cell shape and the potential to move along one direction in another migration mode coined ratchetaxis.

Ends and middle: Global force balance and septum location in fission yeast.

The fission yeast cell is shaped as a very regular cylinder ending by hemi-spheres at both cell ends. Its conserved phenotypes are often used as read-outs for classifying interacting genes and protein networks. Using Pascal and Young-Laplace laws, we proposed a framework where scaling arguments predicted shapes.

How to orient cells in microcavities for high resolution imaging of cytokinesis and lumen formation.

Imaging dynamics of cellular morphogenesis with high spatial-temporal resolution in 3D is challenging, due to the low spatial resolution along the optical axis and photo-toxicity. However, some cellular structures are planar and hence 2D imaging should be sufficient, provided that the structure of interest can be oriented with respect to the optical axis of the microscope. Here, we report a 3D microfabrication method which positions and orients cell divisions very close to the microscope coverglass.

Generation of fluorescent cell-derived-matrix to study 3D cell migration.

Cell migration is involved in key phenomena in biology, ranging from development to cancer. Fibroblasts move between organs in 3D polymeric networks. So far, motile cells were mainly tracked in vitro on Petri dishes or on coverslips, i.

Directing cell migration on flat substrates and in confinement with microfabrication and microfluidics.

Cell motility has been mainly characterized in vitro through the motion of cells on 2D flat Petri dishes, and in Boyden chambers with the passage of cells through sub-cellular sized cavities. These experimental conditions have contributed to understand important features, but these artificial designs can prevent elucidation of mechanisms involved in guiding cell migration in vivo. In this context, microfabrication and microfluidics have provided unprecedented tools to design new assays with local controls in two and three dimensions.

Spatial Fluctuations at Vertices of Epithelial Layers: Quantification of Regulation by Rho Pathway.

In living matter, shape fluctuations induced by acto-myosin are usually studied in vitro via reconstituted gels, whose properties are controlled by changing the concentrations of actin, myosin, and cross-linkers. Such an approach deliberately avoids consideration of the complexity of biochemical signaling inherent to living systems. Acto-myosin activity inside living cells is mainly regulated by the Rho signaling pathway, which is composed of multiple layers of coupled activators and inhibitors.

An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse.

Hemidesmosomes (HDs) are epithelial-specific cell-matrix adhesions that stably anchor the intracellular keratin network to the extracellular matrix. Although their main role is to protect the epithelial sheet from external mechanical strain, how HDs respond to mechanical stress remains poorly understood. Here we identify a pathway essential for HD remodeling and outline its role with respect to α6β4 integrin recycling.

'The Forms of Tissues, or Cell-aggregates': D'Arcy Thompson's influence and its limits.

In two chapters of his book , D'Arcy Thompson used numerous biological and physical observations to show how principles from mathematics and physics - such as pressure differences, surface tension and viscosity - could explain cell shapes and packing within tissues. In this Review, we depict influences that enabled the genesis of his ideas, report examples of his visionary observations and trace his impact over the past 100 years. Recently, his ideas have been revisited as a new field of research emerged, linking cell-level physics with epithelial tissue structure and development.

Interface between Physics and Biology: Training a New Generation of Creative Bilingual Scientists.

Whereas physics seeks for universal laws underlying natural phenomena, biology accounts for complexity and specificity of molecular details. Contemporary biological physics requires people capable of working at this interface. New programs prepare scientists who transform respective disciplinary views into innovative approaches for solving outstanding problems in the life sciences.

Ordering Single Cells and Single Embryos in 3D Confinement: A New Device for High Content Screening.

Biological cells are usually observed on flat (2D) surfaces. This condition is not physiological, and phenotypes and shapes are highly variable. Screening based on cells in such environments have therefore serious limitations: cell organelles show extreme phenotypes, cell morphologies and sizes are heterogeneous and/or specific cell organelles cannot be properly visualized.

Still and rotating myosin clusters determine cytokinetic ring constriction.

The cytokinetic ring is essential for separating daughter cells during division. It consists of actin filaments and myosin motors that are generally assumed to organize as sarcomeres similar to skeletal muscles. However, direct evidence is lacking.

Ratchetaxis: Long-Range Directed Cell Migration by Local Cues.

Directed cell migration is usually thought to depend on the presence of long-range gradients of either chemoattractants or physical properties such as stiffness or adhesion. However, in vivo, chemical or mechanical gradients have not systematically been observed. Here we review recent in vitro experiments, which show that other types of spatial guidance cues can bias cell motility.

Theoretical study of actin layers attachment and separation.

We use the theory of active gels to study theoretically the merging and separation of two actin dense layers akin to cortical layers of animal cells. The layers bind at a distance equal to twice the thickness of a free layer, thus forming a single dense layer, similar in this sense to a lamellipodium. When that unique layer is stretched apart, it is resilient to break apart up to a critical length larger than twice the thickness of a free layer.

The cell ratchet: interplay between efficient protrusions and adhesion determines cell motion.

Many physiological and pathological processes involve directed cell motion. In general, migrating cells are represented with a polarized morphology with extending and retracting protrusions at the leading edge. However, cell motion is a more complex phenomenon.

Synthetic polyamines: new compounds specific to actin dynamics for mammalian cell and fission yeast.

Actin is a major actor in the determination of cell shape. On the one hand, site-directed assembly/disassembly cycles of actin filaments drive protrusive force leading to lamellipodia and filopodia dynamics. Force produced by actin similarly contributes in membrane scission in endocytosis or Golgi remodeling.