How stigmergy in the termite-sand system (left) and in the protocell (right) leads to the formation of new structures. Photo credits: MPI for Molecular Physiology
Nature is full of fascinating patterns. Plants show a beautiful spiral-shaped growth, regularly arranged leaves and petals, animals impress with their striped and spotted fur and social insects build complex nest structures. These almost perfectly arranged patterns seem to arise without a blueprint, like the formation of cell shapes during embryonic development, which is called morphogenesis. An interdisciplinary research team led by Philippe Bastiaens, Director at the Max Planck Institute for Molecular Physiology in Dortmund, has created a lifelike protocell that is energized by chemical potential and is able to convert external signals into changes in shape based on its own self-organized morphology . The team has thus shown how the collective dynamics of nanometer-sized macromolecules organize themselves in micrometer patterns that influence the cellular perception of shape-changing extracellular cues in our own cells. This interdependence between form and information processing, mediated by the deformable plasma membrane, is a fundamental characteristic of living cells and enables them to react to a constantly changing environment depending on their previous experience.
Seemingly headless, thousands of termites crawl across the ground, carrying grains of sand and dropping them. And although the termites have no blueprint, a regular pattern of pillars of sand appears out of nowhere. In this termite-sand system, the termites provide the energy to restructure the sand into a living, dynamic building that is constantly coupled to a constantly changing environment.
Bastiaens’ interdisciplinary group of biochemists and applied and theoretical physicists has now shown that a very similar situation occurs in our cells that use chemical potentials as an energy source to create dynamically maintained structures from molecules instead of grains of sand. The unbalanced, energized state that enables this collective behavior is a property of living matter to create and stabilize a dynamically maintained identity in an ever-changing world.
How form emerges from seeming chance
A characteristic of self-organizing processes are random fluctuations that can be amplified by local interactions between agents. For example, when termites do their random walks, they pick up grains of sand and drop them, causing fluctuations in sand density. However, while stirring the sand, the termites leave a pheromone scent on the grains of sand they have been carrying around, increasing the drop chances of another laden termite passing by by accident. This leads to self-reinforcement of sand piles, which depletes the free grains of sand. The process of reinforcement and exhaustion results in a regular pattern of pillars of sand that forms the basis of their nest.
This phenomenon, known as stigmergy, which means “leaving a mark for work in progress”, was first described in 1959 by the French zoologist Pierre-Paul Grassé and explains how the indirect communication of social insects via sand leads to collective behavior Generating dynamic structures like sand pillars that are regularly organized. The termite queen communicates with this self-organizing termite-sand system by emitting a pheromone gradient. This serves as a template to build a dynamic building around them that adapts to their growing size.
Molecular self-organization brings cells into shape
In order to investigate whether the principles of the stigmergic collective behavior of the termite-sand system also apply to the self-organization of biomolecules in cellular morphogenesis, Bastiaens’s group builds a synthetic cell with lifelike properties by converting lifeless biological building blocks into a deformable one Lipid membrane and bring it to life by energizing the system with the chemical potential of ATP / GTP. This now out of equilibrium encapsulated system consisted of a dynamic microtubule cytoskeleton and a light-sensitive molecular signal module that works in a similar way to natural morphogen signaling.
In cellular morphogenesis, new structures are created through the deformation of the plasma membrane through dynamic rearrangements of the cytoskeleton. Extracellular morphogens control this process by binding to receptors on the cell membrane. Information is transmitted within the cell by rebalancing the intracellular phosphorylation reaction cycles. This creates intracellular chemical signal gradients that promote the growth of the cytoskeleton locally. Scientists recreated this process by developing a light-responsive signaling system that translocates a bioengineered kinase to the membrane that rebalances the phosphorylation reaction cycles of the tubulin sequestering molecule stathmin. They were able to show that cytoskeletal growth is actually promoted by the fact that these phosphorylation cycles function like a molecular machine that continuously pumps microtubule components to the membrane.
Stigmerge principles in cellular morphogenesis
The scientists’ ideas turned out to be true, because their lifelike protocells showed that both the cytoskeleton and the signaling system organize themselves into different patterns through interaction with the membrane according to the same stigmergen principles as the termites themselves. Sand system. In the case of the cytoskeleton, a small protrusion of the membrane formed by the local growth of a microtubule traps more microtubules, thereby increasing the growth of the protrusion that depletes the free microtubules. In the case of the signaling system, the recruitment of the kinase to the membrane leads to self-amplified clusters that consume the free kinase.
In addition, the researchers were able to show that the indirect communication between the signaling and the cytoskeletal system was mediated by the deformable membrane, which led to self-organized shapes such as star-shaped or polar structures. They were also able to show that localized extracellular signal signals act similarly to the pheromone-emitting termite queen, providing a chemical template that directs the self-organizing termite-sand system so that a dynamic building is structured around them. In the case of protocells, the signal gradient restricted the self-organizing solutions of the bidirectionally communicating signal and cytoskeletal systems to reorganize the lifelike cells in the direction of extracellular signals. However, this response to extracellular signals was very much dependent on the initial, self-organized shape of the protocells, which makes their response subjective to the previous experience that shaped them.
Cellular perception arises from the interdependence of form and signaling
It turned out that the equilibrium of the two recursively interacting stigmergic systems determined the basal morphology of the protocell, for example whether it was polar or star-shaped. When the basal signal transduction dominated the microtubule-induced membrane deformation, the protocells showed a star-like morphology, while the protocells became polar when the microtubule-induced deformation dominated the signal transduction. Changing the balance between the stigmergic systems through an extracellular signal can transform a star into a polar shape, but not the other way around. This shows that the morphing of cells is not only controlled by a unidirectional flow of information from extracellular cues, but is also determined by the morphology of the cell itself, which is shaped by previous events.
“Whether cells in a developing healthy or diseased tissue react to their environment depending on previous experience is a big question in the field of cell and developmental biology. Our work shows that cells do not behave like simple input-output machines, but rather integrate previous “experiences in their reaction to a constantly changing environment. In a developing tissue, the environment of the cells consists of other cells and our self-organized protocells have the potential, via the property of mechanosensors, resulting from the recursive coupling between the signaling and cytoskeletal system. This would allow us to investigate how recursive communication between self-organized molecular systems within cells leads to self-organized tissue formation on a larger scale, ”concludes Philippe Bastiaens.
A deeper understanding of how cells move and hold together
More information:
Konstantin Gavriljuk et al., A self-assembled synthetic morphogenic liposome reacts with changes in shape to local light signals, Nature Communications (2021). DOI: 10.1038 / s41467-021-21679-2 Provided by the Max Planck Society
Quote: What termites and cells have in common (2021, June 25), accessed June 25, 2021 from https://phys.org/news/2021-06-termites-cells-common.html
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