Single-celled organism uses internal 'computer' to walk
https://reasonandscience.catsboard.com/t3263-single-celled-organism-uses-internal-computer-to-walk
Most animals require brains to run, jump or hop. The single-celled protozoan Euplotes eurystomus, however, achieves a scurrying walk using a simple, mechanical computer to coordinate its microscopic legs, UC San Francisco researchers reported on September 22, 2022, in the journal Current Biology.
Euplotes has 14 leg-like appendages, each one composed of bundles of hair-like cilia. The researchers showed for the first time that internal connections between these cilia control their motions, letting the legs move only in certain patterns and sequences. When these internal connections are disrupted, the movements of the aquatic organisms become less productive—often leading the cells to turn in circles rather than walk in a line.
"Euplotes uses these connections to facilitate an elaborate walking motion, but my suspicion is when we delve into this more, we'll find that other cells use similar forms of computation to control more subtle processes," said Wallace Marshall, Ph.D., lead study author and professor of biochemistry and biophysics at UCSF.
In general, aquatic single-celled organisms don't have legs and don't walk—they roll, swim or slither. So when UCSF postdoctoral research fellow Ben Larson, Ph.D. spotted Euplotes scurrying around under his microscope, he at first thought he was watching insect-like animals. When he realized the organisms were single-celled, he became intrigued by how they coordinated their 14 appendages without a brain or nervous system.
To understand this unusual ability, Larson and Marshall watched Euplotes cells in more detail, slowing down videos of the walking cells, capturing 33 frames per second, and labeling each leg to analyze the organisms' gait.
"There seemed to be this sequential logic happening with the movements," said Larson. "They weren't random, and we began to suspect there was some sort of information processing happening."
A microtubule machine
Scientists had known since the 1920s that long protein filaments projected into Euplotes from each of its appendages. Composed of microtubules—the main component of a cell's scaffolding, or cytoskeleton—these filaments were long assumed to play a structural role in Euplotes. But when Larson and Marshall disrupted the microtubules with a drug or by cutting them with a needle, Euplotes no longer walked in the same way; its movements became more random and haphazard.
The researchers teamed up with computer scientists to model how the filaments could be controlling the walking motion. Together, they concluded that tension and strain on the filaments could dictate which gait states were possible at any given moment. The machinery, they said, resembles a Strandbeest—a moving, kinetic sculpture designed by a Dutch artist to walk and react to its environment.
Although this kind of internal machinery doesn't resemble today's digital devices, it does follow principles used by early mechanical computers, Marshall said.
"The fact that Euplotes' appendages are moving from one state to another in a non-random way means this system is like a rudimentary computer," he said.
More work is needed to understand exactly how the microtubule filaments control Euplotes walk, the researchers admit. But their computational modeling and experiments suggest a completely new, mechanical method for a cell to control its internal state.
"This is a really fascinating biological phenomenon itself, but also could highlight more general computational processes in other types of cells," said Larson. 1
Ben T. Larson (2022): Cells are complex biochemical systems whose behaviors emerge from interactions among myriad molecular components. Computation is often invoked as a general framework for navigating this cellular complexity. However, it is unclear how cells might embody computational processes such that the theories of computation, including finite-state machine models, could be productively applied. Here, we demonstrate finite-state-machine-like processing embodied in cells using the walking behavior of Euplotes eurystomus, a ciliate that walks across surfaces using fourteen motile appendages (cirri). We found that cellular walking entails regulated transitions among a discrete set of gait states. The set of observed transitions decomposes into a small group of high-probability, temporally irreversible transitions and a large group of low-probability, time-symmetric transitions, thus revealing stereotypy in the sequential patterns of state transitions. Simulations and experiments suggest that the sequential logic of the gait is functionally important. Taken together, these findings implicate a finite-state-machine-like process. Cirri are connected by microtubule bundles (fibers), and we found that the dynamics of cirri involved in different state transitions are associated with the structure of the fiber system. Perturbative experiments revealed that the fibers mediate gait coordination, suggesting a mechanical basis of gait control.
It has been argued that physical systems exhibiting such a mix of stereotypy and variability can be viewed as performing computations in the sense that the evolution of the system over time is most compactly described as the result of a computational process involving state transitions, memory, and decision rules.
Cells are complex physical systems controlled by networks of signaling molecules. Single cells can display sophisticated, animal-like behaviors, orchestrating active processes far from thermodynamic equilibrium in order to properly carry out biological functions. Indeed, single cells can make decisions, execute coordinated, directed movements, solve mazes, and learn. Such behaviors in animals arise from neural activity, but we know comparatively little about the mechanisms of cellular behavior, which emerge from a combination of chemical reactions, cellular architecture, physical constraints, and interactions with the environment. The involvement of information processing in cell state transitions suggest that cellular behavior can be understood as an embodied computation. The theory of computation has often been invoked as a general framework for understanding cellular dynamics—environmental sensing by bacteria being a deeply studied example—and has been used to engineer programmable cell states. Ciliates display some of the most striking examples of unicellular behavior, including hunting, sensorimotor navigation, and predator avoidance. Spirotrichous ciliates of the genus Euplotes are notable for their complex locomotion, using bundles of specialized cilia (cirri) to walk across surfaces. Depending on the species, these cells generally have 14 to 15 ventral cirri arranged in a consistent pattern used for walking locomotion. Euplotes live in aquatic environments and, in addition to walking, use their cirri for swimming and rapid escape responses. Oral membranelles are also used for swimming and to generate feeding currents for capturing bacterial and protistan prey. Early 20th century protistologists were so impressed by the apparent coordination of cirri that they proposed the existence of a rudimentary nervous system, the neuromotor apparatus, to account for their observations. This theory was motivated by the presence of tubulin-based intracellular fibers emanating from the bases of cirri.
How can a single cell coordinate a walking gait without a nervous system? Coordination, to the extent that it exists in the gait of Euplotes, requires dynamical coupling among cirri or between cirri and some shared external influence. Although the walking movements of Euplotes appear superficially similar to those of animals such as insects, the existence of stereotyped sequences of appendage movements that define a gait is unclear. Systems that violate detailed balance operate in a non-equilibrium mode, display net probability flows, and can produce directed cycles in state space.
When information processing drives patterns of state transitions, such a system can be analyzed using automata theory, a fundamental level in the theory of computation. We hypothesized that walking cells might be governed by finite-state automata with directed, processive movement arising from reproducible, stereotyped patterns of state transitions. We chose to focus on the relatively simple case of spontaneous linear walking, which might require some form of information processing to coordinate the movements of cirri.
Traditionally, studies of computational processes in cells have focused on combinatorial logic, in which a molecular network generates an output that depends only on the current input. We have focused on sequential logic, in which outputs depend on the system state as well. Automata theory, using finite-state machine models based on sequential logic, provides tools for understanding structure and stereotypy in transitions between dynamical states, which are increasingly appreciated as features of the behavior of eukaryotic cells. Related approaches for the coarse-graining of complex dynamics have revealed simplicity and stereotypy in the behavior patterns of various organisms. Although there are examples of locomotor coordination reminiscent of the stochastic, non-equilibrium gait dynamics of Euplotes in other cells and animals, most appendage-based locomotor systems employ stereotyped, determinate patterns of activity. In the run-and-tumble motility in Escherichia coli or analogous behaviors observed in protists, motility can be described by equilibrium processes, in contrast to the non-equilibrium character of the gait of Euplotes.
We propose that in Euplotes, biased, actively controlled cyclic transitions store stress in certain cirri, and the spontaneous release of these cirri from the substrate, during a series of unbiased gait state transitions, allows the cell to move forward. Return to the cycle states reset this process by winding up the system for continued, proper cell movement.
The results of experiments perturbing the tubulin-based cytoskeletal fiber system are consistent with its role in mechanically mediating communication both among cirri and between cirri and the cell cortex. We conjecture that movement of cirri relative to one another can establish tension in the fiber system and that the tension state of fibers associated with each cirrus may then modulate cirral activity in a manner reminiscent of basal coupling in flagellates. Microtubules can respond directly to mechanical forces inside cells and may be involved in more complex signal-transduction pathways. Our results show that perturbation of the microtubule fiber system shift the gait of Euplotes from a regime of asynchronous yet coordinated movements to a dysregulated regime with synchronous yet improperly coordinated movements. Our work lays a foundation for studying sensorimotor behavior in Euplotes, which will shed light on principles of cellular behavior. 2
1. Sarah C.P. Williams: Single-celled organism uses internal 'computer' to walk OCTOBER 11, 2022
2. Ben T. Larson: A unicellular walker controlled by a microtubule-based finite-state machine SEPTEMBER 12, 2022
https://reasonandscience.catsboard.com/t3263-single-celled-organism-uses-internal-computer-to-walk
Most animals require brains to run, jump or hop. The single-celled protozoan Euplotes eurystomus, however, achieves a scurrying walk using a simple, mechanical computer to coordinate its microscopic legs, UC San Francisco researchers reported on September 22, 2022, in the journal Current Biology.
Euplotes has 14 leg-like appendages, each one composed of bundles of hair-like cilia. The researchers showed for the first time that internal connections between these cilia control their motions, letting the legs move only in certain patterns and sequences. When these internal connections are disrupted, the movements of the aquatic organisms become less productive—often leading the cells to turn in circles rather than walk in a line.
"Euplotes uses these connections to facilitate an elaborate walking motion, but my suspicion is when we delve into this more, we'll find that other cells use similar forms of computation to control more subtle processes," said Wallace Marshall, Ph.D., lead study author and professor of biochemistry and biophysics at UCSF.
In general, aquatic single-celled organisms don't have legs and don't walk—they roll, swim or slither. So when UCSF postdoctoral research fellow Ben Larson, Ph.D. spotted Euplotes scurrying around under his microscope, he at first thought he was watching insect-like animals. When he realized the organisms were single-celled, he became intrigued by how they coordinated their 14 appendages without a brain or nervous system.
To understand this unusual ability, Larson and Marshall watched Euplotes cells in more detail, slowing down videos of the walking cells, capturing 33 frames per second, and labeling each leg to analyze the organisms' gait.
The cells didn't walk like people, with legs clearly alternating, nor did they have a cadence like a galloping horse. But Larson and Marshall found that the appendages did follow certain patterns. The researchers characterized 32 different "gait states," or combinations of leg movements, and then showed that certain gait states were more likely to follow others.
A microtubule machine
Scientists had known since the 1920s that long protein filaments projected into Euplotes from each of its appendages. Composed of microtubules—the main component of a cell's scaffolding, or cytoskeleton—these filaments were long assumed to play a structural role in Euplotes. But when Larson and Marshall disrupted the microtubules with a drug or by cutting them with a needle, Euplotes no longer walked in the same way; its movements became more random and haphazard.
The researchers teamed up with computer scientists to model how the filaments could be controlling the walking motion. Together, they concluded that tension and strain on the filaments could dictate which gait states were possible at any given moment. The machinery, they said, resembles a Strandbeest—a moving, kinetic sculpture designed by a Dutch artist to walk and react to its environment.
A single Euplotes walking under a microscope, using its "legs." The video is slowed down by a factor of 4 to make the movements more clearly visible. Credit: Ben Larson/Wallace Lab
"The fact that Euplotes' appendages are moving from one state to another in a non-random way means this system is like a rudimentary computer," he said.
More work is needed to understand exactly how the microtubule filaments control Euplotes walk, the researchers admit. But their computational modeling and experiments suggest a completely new, mechanical method for a cell to control its internal state.
"This is a really fascinating biological phenomenon itself, but also could highlight more general computational processes in other types of cells," said Larson. 1
Ben T. Larson (2022): Cells are complex biochemical systems whose behaviors emerge from interactions among myriad molecular components. Computation is often invoked as a general framework for navigating this cellular complexity. However, it is unclear how cells might embody computational processes such that the theories of computation, including finite-state machine models, could be productively applied. Here, we demonstrate finite-state-machine-like processing embodied in cells using the walking behavior of Euplotes eurystomus, a ciliate that walks across surfaces using fourteen motile appendages (cirri). We found that cellular walking entails regulated transitions among a discrete set of gait states. The set of observed transitions decomposes into a small group of high-probability, temporally irreversible transitions and a large group of low-probability, time-symmetric transitions, thus revealing stereotypy in the sequential patterns of state transitions. Simulations and experiments suggest that the sequential logic of the gait is functionally important. Taken together, these findings implicate a finite-state-machine-like process. Cirri are connected by microtubule bundles (fibers), and we found that the dynamics of cirri involved in different state transitions are associated with the structure of the fiber system. Perturbative experiments revealed that the fibers mediate gait coordination, suggesting a mechanical basis of gait control.
It has been argued that physical systems exhibiting such a mix of stereotypy and variability can be viewed as performing computations in the sense that the evolution of the system over time is most compactly described as the result of a computational process involving state transitions, memory, and decision rules.
Cells are complex physical systems controlled by networks of signaling molecules. Single cells can display sophisticated, animal-like behaviors, orchestrating active processes far from thermodynamic equilibrium in order to properly carry out biological functions. Indeed, single cells can make decisions, execute coordinated, directed movements, solve mazes, and learn. Such behaviors in animals arise from neural activity, but we know comparatively little about the mechanisms of cellular behavior, which emerge from a combination of chemical reactions, cellular architecture, physical constraints, and interactions with the environment. The involvement of information processing in cell state transitions suggest that cellular behavior can be understood as an embodied computation. The theory of computation has often been invoked as a general framework for understanding cellular dynamics—environmental sensing by bacteria being a deeply studied example—and has been used to engineer programmable cell states. Ciliates display some of the most striking examples of unicellular behavior, including hunting, sensorimotor navigation, and predator avoidance. Spirotrichous ciliates of the genus Euplotes are notable for their complex locomotion, using bundles of specialized cilia (cirri) to walk across surfaces. Depending on the species, these cells generally have 14 to 15 ventral cirri arranged in a consistent pattern used for walking locomotion. Euplotes live in aquatic environments and, in addition to walking, use their cirri for swimming and rapid escape responses. Oral membranelles are also used for swimming and to generate feeding currents for capturing bacterial and protistan prey. Early 20th century protistologists were so impressed by the apparent coordination of cirri that they proposed the existence of a rudimentary nervous system, the neuromotor apparatus, to account for their observations. This theory was motivated by the presence of tubulin-based intracellular fibers emanating from the bases of cirri.
How can a single cell coordinate a walking gait without a nervous system? Coordination, to the extent that it exists in the gait of Euplotes, requires dynamical coupling among cirri or between cirri and some shared external influence. Although the walking movements of Euplotes appear superficially similar to those of animals such as insects, the existence of stereotyped sequences of appendage movements that define a gait is unclear. Systems that violate detailed balance operate in a non-equilibrium mode, display net probability flows, and can produce directed cycles in state space.
When information processing drives patterns of state transitions, such a system can be analyzed using automata theory, a fundamental level in the theory of computation. We hypothesized that walking cells might be governed by finite-state automata with directed, processive movement arising from reproducible, stereotyped patterns of state transitions. We chose to focus on the relatively simple case of spontaneous linear walking, which might require some form of information processing to coordinate the movements of cirri.
Traditionally, studies of computational processes in cells have focused on combinatorial logic, in which a molecular network generates an output that depends only on the current input. We have focused on sequential logic, in which outputs depend on the system state as well. Automata theory, using finite-state machine models based on sequential logic, provides tools for understanding structure and stereotypy in transitions between dynamical states, which are increasingly appreciated as features of the behavior of eukaryotic cells. Related approaches for the coarse-graining of complex dynamics have revealed simplicity and stereotypy in the behavior patterns of various organisms. Although there are examples of locomotor coordination reminiscent of the stochastic, non-equilibrium gait dynamics of Euplotes in other cells and animals, most appendage-based locomotor systems employ stereotyped, determinate patterns of activity. In the run-and-tumble motility in Escherichia coli or analogous behaviors observed in protists, motility can be described by equilibrium processes, in contrast to the non-equilibrium character of the gait of Euplotes.
We propose that in Euplotes, biased, actively controlled cyclic transitions store stress in certain cirri, and the spontaneous release of these cirri from the substrate, during a series of unbiased gait state transitions, allows the cell to move forward. Return to the cycle states reset this process by winding up the system for continued, proper cell movement.
The results of experiments perturbing the tubulin-based cytoskeletal fiber system are consistent with its role in mechanically mediating communication both among cirri and between cirri and the cell cortex. We conjecture that movement of cirri relative to one another can establish tension in the fiber system and that the tension state of fibers associated with each cirrus may then modulate cirral activity in a manner reminiscent of basal coupling in flagellates. Microtubules can respond directly to mechanical forces inside cells and may be involved in more complex signal-transduction pathways. Our results show that perturbation of the microtubule fiber system shift the gait of Euplotes from a regime of asynchronous yet coordinated movements to a dysregulated regime with synchronous yet improperly coordinated movements. Our work lays a foundation for studying sensorimotor behavior in Euplotes, which will shed light on principles of cellular behavior. 2
1. Sarah C.P. Williams: Single-celled organism uses internal 'computer' to walk OCTOBER 11, 2022
2. Ben T. Larson: A unicellular walker controlled by a microtubule-based finite-state machine SEPTEMBER 12, 2022
