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Emergent systems energy laws for predicting myosin ensemble processivity.

Egan P, Moore J, Schunn C, Cagan J, LeDuc P - PLoS Comput. Biol. (2015)

Bottom Line: On the basis of prior experimental evidence that longer processive lifetimes are enabled by larger myosin ensembles, it is hypothesized that emergent scaling laws could coincide with myosin-actin contact probability or system energy consumption.Because processivity is difficult to predict analytically and measure experimentally, agent-based computational techniques are developed to simulate processive myosin ensembles and produce novel processive lifetime measurements.It is demonstrated that only systems energy relationships hold regardless of isoform configurations or ensemble size, and a unified expression for predicting processive lifetime is revealed.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.

ABSTRACT
In complex systems with stochastic components, systems laws often emerge that describe higher level behavior regardless of lower level component configurations. In this paper, emergent laws for describing mechanochemical systems are investigated for processive myosin-actin motility systems. On the basis of prior experimental evidence that longer processive lifetimes are enabled by larger myosin ensembles, it is hypothesized that emergent scaling laws could coincide with myosin-actin contact probability or system energy consumption. Because processivity is difficult to predict analytically and measure experimentally, agent-based computational techniques are developed to simulate processive myosin ensembles and produce novel processive lifetime measurements. It is demonstrated that only systems energy relationships hold regardless of isoform configurations or ensemble size, and a unified expression for predicting processive lifetime is revealed. The finding of such laws provides insight for how patterns emerge in stochastic mechanochemical systems, while also informing understanding and engineering of complex biological systems.

No MeSH data available.


Related in: MedlinePlus

Schematic of processive myosin system with dissociation.Schematic of a myosin ensemble propelling actin at unloaded velocity vu. Myosin states are stochastic, with myosins being detached, attached and power-stroking (light yellow point of contact), or attached and drag-stroking (dark red point of contact). Initially three myosins are attached (top); later the filament has translated and one myosin is attached (middle); at processivity termination, all myosins are detached (bottom).
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pcbi.1004177.g001: Schematic of processive myosin system with dissociation.Schematic of a myosin ensemble propelling actin at unloaded velocity vu. Myosin states are stochastic, with myosins being detached, attached and power-stroking (light yellow point of contact), or attached and drag-stroking (dark red point of contact). Initially three myosins are attached (top); later the filament has translated and one myosin is attached (middle); at processivity termination, all myosins are detached (bottom).

Mentions: In both natural and engineered myosin systems, functionality often emerges from the processive transport of actin filaments relative to stationary myosins; a minimum number of myosins are required to ensure a filament continues with a consistent trajectory and velocity. Consistency in processivity is measurable through considering a system’s processive lifetime , which refers to the duration from initial myosin-actin contact until system dissociation occurs during periods when no myosins are in contact with actin (Fig 1) [19]. Processivity is an essential metric to consider in the design of myosin-based nanotechnologies that operate on similar principles as motility assays [20]. Motility assays are common experiments for investigating how individual myosin configuration affects system behavior, and these experiments often measure the velocity of actin filaments propelled by a bed of myosins [21]. Typically, there is a negligible load assumed to act on the actin filament, which is representative of physiological situations with low external loads or nanotechnologies that operate in similar controlled environments. Although many models and simulations exist for myosin systems [5,22–24], they mostly concentrate on physiological models rather than motility assays. The simulation of motility assays, however, enables the experimental investigation of phenomenon such as how myosin isoform configuration affects the maximum achievable filament velocity and probability of contact among myosins and actin, which is suggestive of the potential loaded system capabilities. We therefore concentrate on building models and simulations of motility assays as a basis for investigating emergent system laws informed by fundamental biophysical experiments.


Emergent systems energy laws for predicting myosin ensemble processivity.

Egan P, Moore J, Schunn C, Cagan J, LeDuc P - PLoS Comput. Biol. (2015)

Schematic of processive myosin system with dissociation.Schematic of a myosin ensemble propelling actin at unloaded velocity vu. Myosin states are stochastic, with myosins being detached, attached and power-stroking (light yellow point of contact), or attached and drag-stroking (dark red point of contact). Initially three myosins are attached (top); later the filament has translated and one myosin is attached (middle); at processivity termination, all myosins are detached (bottom).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401713&req=5

pcbi.1004177.g001: Schematic of processive myosin system with dissociation.Schematic of a myosin ensemble propelling actin at unloaded velocity vu. Myosin states are stochastic, with myosins being detached, attached and power-stroking (light yellow point of contact), or attached and drag-stroking (dark red point of contact). Initially three myosins are attached (top); later the filament has translated and one myosin is attached (middle); at processivity termination, all myosins are detached (bottom).
Mentions: In both natural and engineered myosin systems, functionality often emerges from the processive transport of actin filaments relative to stationary myosins; a minimum number of myosins are required to ensure a filament continues with a consistent trajectory and velocity. Consistency in processivity is measurable through considering a system’s processive lifetime , which refers to the duration from initial myosin-actin contact until system dissociation occurs during periods when no myosins are in contact with actin (Fig 1) [19]. Processivity is an essential metric to consider in the design of myosin-based nanotechnologies that operate on similar principles as motility assays [20]. Motility assays are common experiments for investigating how individual myosin configuration affects system behavior, and these experiments often measure the velocity of actin filaments propelled by a bed of myosins [21]. Typically, there is a negligible load assumed to act on the actin filament, which is representative of physiological situations with low external loads or nanotechnologies that operate in similar controlled environments. Although many models and simulations exist for myosin systems [5,22–24], they mostly concentrate on physiological models rather than motility assays. The simulation of motility assays, however, enables the experimental investigation of phenomenon such as how myosin isoform configuration affects the maximum achievable filament velocity and probability of contact among myosins and actin, which is suggestive of the potential loaded system capabilities. We therefore concentrate on building models and simulations of motility assays as a basis for investigating emergent system laws informed by fundamental biophysical experiments.

Bottom Line: On the basis of prior experimental evidence that longer processive lifetimes are enabled by larger myosin ensembles, it is hypothesized that emergent scaling laws could coincide with myosin-actin contact probability or system energy consumption.Because processivity is difficult to predict analytically and measure experimentally, agent-based computational techniques are developed to simulate processive myosin ensembles and produce novel processive lifetime measurements.It is demonstrated that only systems energy relationships hold regardless of isoform configurations or ensemble size, and a unified expression for predicting processive lifetime is revealed.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.

ABSTRACT
In complex systems with stochastic components, systems laws often emerge that describe higher level behavior regardless of lower level component configurations. In this paper, emergent laws for describing mechanochemical systems are investigated for processive myosin-actin motility systems. On the basis of prior experimental evidence that longer processive lifetimes are enabled by larger myosin ensembles, it is hypothesized that emergent scaling laws could coincide with myosin-actin contact probability or system energy consumption. Because processivity is difficult to predict analytically and measure experimentally, agent-based computational techniques are developed to simulate processive myosin ensembles and produce novel processive lifetime measurements. It is demonstrated that only systems energy relationships hold regardless of isoform configurations or ensemble size, and a unified expression for predicting processive lifetime is revealed. The finding of such laws provides insight for how patterns emerge in stochastic mechanochemical systems, while also informing understanding and engineering of complex biological systems.

No MeSH data available.


Related in: MedlinePlus