Cytoskeletal symmetry breaking in animal cells.

Symmetry breaking is a crucial step in structure formation and function of all cells, necessary for cell movement, cell division, and polarity establishment. Although the mechanisms of symmetry breaking are diverse, they often share common characteristics. Here we review examples of nematic, polar, and chiral cytoskeletal symmetry breaking in animal cells, and analogous processes in simplified reconstituted systems. We discuss the origins of symmetry breaking, which can arise spontaneously, or involve amplification of a pre-existing external or internal bias to the whole cell level. The underlying mechanisms often involve both chemical and mechanical processes that cooperate to break symmetry in a robust manner, and typically depend on the shape, size, or properties of the cell's boundary.

Centering and symmetry breaking in confined contracting actomyosin networks.

Centering and decentering of cellular components is essential for internal organization of cells and their ability to perform basic cellular functions such as division and motility. How cells achieve proper localization of their organelles is still not well-understood, especially in large cells such as oocytes. Here, we study actin-based positioning mechanisms in artificial cells with persistently contracting actomyosin networks, generated by encapsulating cytoplasmic Xenopus egg extracts into cell-sized 'water-in-oil' droplets. We observe size-dependent localization of the contraction center, with a symmetric configuration in larger cells and a polar one in smaller cells. Centering is achieved via a hydrodynamic mechanism based on Darcy friction between the contracting network and the surrounding cytoplasm. During symmetry breaking, transient attachments to the cell boundary drive the contraction center to a polar location. The centering mechanism is cell-cycle dependent and weakens considerably during interphase. Our findings demonstrate a robust, yet tunable, mechanism for subcellular localization.

In order to survive, cells need to react to their environment and change their shape or the localization of their internal components. For example, the nucleus ­ the compartment that contains the genetic information ­ is often localized at the center of the cell, but it can also be positioned at the side, for instance when cells move or divide asymmetrically. Cells use multiple positioning mechanisms to move their internal components, including a process that relies on networks of filaments made of a protein known as actin. These networks are constantly remodeled as actin proteins are added and removed from the network. Embedded molecular motors can cause the network of actin filaments to contract and push or pull on the compartments. Yet, the exact way these networks localize components in the cell remains unclear, especially in eggs and other large cells. To investigate this question, Ierushalmi et al. studied the actin networks in artificial cells that they created by enclosing the contents of frog eggs in small droplets surrounded by oil. This showed that the networks contracted either to the center of the cell or to its side. Friction between the contracting actin network and the fluid in the cell generated a force that tends to push the contraction center towards the middle of the cell. In larger cells, this led to the centering of the actin network. In smaller cells however, the network transiently attached to the boundary of the cell, leading the contraction center to be pulled to one side. By developing simpler artificial cells that mimic the positioning processes seen in real-life cells, Ierushalmi et al. discovered new mechanisms for how cells may center or de-center their components. This knowledge may be useful to understand diseases that can emerge when the nucleus or other compartments fail to move to the right location, and which are associated with certain organs developing incorrectly.

Scaling behaviour in steady-state contracting actomyosin networks.

Contractile actomyosin network flows are crucial for many cellular processes including cell division and motility, morphogenesis and transport. How local remodeling of actin architecture tunes stress production and dissipation and regulates large-scale network flows remains poorly understood. Here, we generate contracting actomyosin networks with rapid turnover in vitro, by encapsulating cytoplasmic Xenopus egg extracts into cell-sized 'water-in-oil' droplets. Within minutes, the networks reach a dynamic steady-state with continuous inward flow. The networks exhibit homogeneous, density-independent contraction for a wide range of physiological conditions, implying that the myosin-generated stress driving contraction and the effective network viscosity have similar density dependence. We further find that the contraction rate is roughly proportional to the network turnover rate, but this relation breaks down in the presence of excessive crosslinking or branching. Our findings suggest that cells use diverse biochemical mechanisms to generate robust, yet tunable, actin flows by regulating two parameters: turnover rate and network geometry.

Cellular Organization: Bulk Actin Network Flows Drive Ooplasm Segregation.

Actin networks in the bulk cytoplasm, rather than cortical dynamics, drive ooplasm segregation in zebrafish oocytes. A contracting actin network drags the ooplasm toward the animal pole, while 'comet tails' push the yolk granules in the opposite direction.