A novel mechanism of self-organization in active matter, crucial for bacterial cell division, has been discovered that operates under the principle of ‘dying to align’. Misaligned filaments naturally ‘perish’ to create a ring structure in the center of the dividing cell. This research, directed by the Å arić group at the Institute of Science and Technology Austria (ISTA), was published in Nature Physics and could lead to advancements in synthetic self-healing materials.
A novel mechanism of self-organization in active matter, crucial for bacterial cell division, has been discovered that operates under the principle of ‘dying to align’. Misaligned filaments naturally ‘perish’ to create a ring structure in the center of the dividing cell. This research, directed by the Å arić group at the Institute of Science and Technology Austria (ISTA), was published in Nature Physics and could lead to advancements in synthetic self-healing materials.
What allows non-living matter to self-organize in ways that bring about life? A key feature of life is self-organization, which involves the spontaneous formation and breakdown of biological active matter. This raises the question of how molecules ‘know’ how, when, and where to assemble, and when to disband.
In their investigation of bacterial cell division, researchers from the Å arić group, including Professor AnÄ‘ela Å arić and PhD candidate Christian Vanhille Campos, developed a computational model to study a protein called FtsZ, which is a form of active matter. During bacterial division, FtsZ self-forms into a ring at the center of the cell. This bacterial division ring is crucial as it helps create a wall separating the new daughter cells. However, many fundamental physical principles of FtsZ’s self-assembly remain unexplained. Now, the Å arić group has collaborated with experimental teams from Séamus Holden’s group at The University of Warwick, UK, and Martin Loose’s group at ISTA to uncover a surprising self-assembly mechanism. Their computational results reveal how misaligned FtsZ filaments respond when they encounter hindrances; they ‘die’ and reassemble, favoring the creation of a well-aligned bacterial division ring. This research could have implications for designing synthetic self-healing materials.
Treadmilling: the adaptive nature of molecular turnover
FtsZ assembles into protein filaments that undergo continuous growth and shrinkage, a process known as ‘treadmilling’. This involves the constant addition and removal of subunits from opposite ends of the filament. Many proteins exhibit treadmilling in various forms of life, including bacteria, animals, and plants. Traditionally, scientists viewed treadmilling as a means of self-propulsion, modeling it as filaments moving forward. However, such models overlook the continuous turnover of subunits and often overstate the forces produced during assembly. Therefore, AnÄ‘ela Å arić and her research team aimed to model the interactions of FtsZ subunits to clarify how they spontaneously generate filaments through treadmilling. “In our cells, everything is in constant flux. We must consider biological active matter from the perspective of molecular turnover and how it adjusts to environmental conditions,” Åžarić explains.
Temporary filaments: dying for alignment
The team’s findings were unexpected. Unlike self-propelling structures that push surrounding molecules and create a ‘bump’ over long distances, misaligned FtsZ filaments began to ‘die’ upon hitting an obstacle. “Active matter made of temporary filaments does not tolerate misalignment well. When a filament grows and collides with barriers, it dissolves and ceases to exist,” notes first author Vanhille Campos. Åžarić adds, “Our model shows that treadmilling assemblies promote local healing of active material. The demise of misaligned filaments contributes to a more cohesive overall assembly.” By integrating the cell’s geometry and filament curvature into their model, they demonstrated how the collapse of misaligned FtsZ filaments facilitates the formation of the bacterial division ring.
Theoretical research validated by experimental collaborations
Guided by physical theories of molecular interactions, Å arić and her team made two pivotal connections with experimental groups that validated their findings. They encountered Séamus Holden, who was working on visualizing bacterial ring formation in live cells, at a multidisciplinary conference titled ‘Physics Meets Biology.’ At this conference, Holden shared fascinating experimental results indicating that the cycle of birth and death of FtsZ filaments is vital for creating the division ring, highlighting the importance of treadmilling. “It was rewarding to see that FtsZ rings in our simulations displayed behavior similar to those observed in Bacillus subtilis division rings by Holden’s team,” Vanhille Campos remarked.
Shifting from University College London to ISTA enabled Å arić to collaborate with Martin Loose, who was studying FtsZ filament assembly in a controlled laboratory setting. They found that the experimental results aligned closely with the simulations, further substantiating their computational findings. Emphasizing the collaborative spirit among the three teams, Åžarić states, “By venturing beyond our usual research domains, we facilitate open discussions, data sharing, and knowledge exchange, enabling us to solve questions that would be challenging individually.”
Towards synthetic self-healing materials
The self-organization of energy-driven matter is a critical process in physics. The Å arić team’s findings suggest that FtsZ filaments represent a unique kind of active matter that invests energy in turnover instead of solely in movement. “In my lab, we explore how to generate living-like matter from non-living materials. Consequently, this research could aid in developing synthetic self-healing materials or artificial cells,” says Åžarić. As a next step, the team aims to model the role of the bacterial division ring in constructing a wall to split the cell into two. Holden and Åžarić plan to further investigate this topic with the support of a recent 3.7 million Euro grant from the Wellcome Trust.
