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Sarcomeric pattern formation by actin cluster coalescence.

Friedrich BM, Fischer-Friedrich E, Gov NS, Safran SA - PLoS Comput. Biol. (2012)

Bottom Line: Using a one-dimensional computational model of an initially unstriated actin bundle, we show that actin filament treadmilling in the presence of processive plus-end crosslinking provides a simple and robust mechanism for the polarity sorting of actin filaments as well as for the correct localization of myosin filaments.In our simulations, sarcomere spacing is set by filament length prompting tight length control already at early stages of pattern formation.The proposed mechanism could be generic and apply both to premyofibrils and nascent myofibrils in developing muscle cells as well as possibly to striated stress-fibers in non-muscle cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot, Israel. ben@pks.mpg.de

ABSTRACT
Contractile function of striated muscle cells depends crucially on the almost crystalline order of actin and myosin filaments in myofibrils, but the physical mechanisms that lead to myofibril assembly remains ill-defined. Passive diffusive sorting of actin filaments into sarcomeric order is kinetically impossible, suggesting a pivotal role of active processes in sarcomeric pattern formation. Using a one-dimensional computational model of an initially unstriated actin bundle, we show that actin filament treadmilling in the presence of processive plus-end crosslinking provides a simple and robust mechanism for the polarity sorting of actin filaments as well as for the correct localization of myosin filaments. We propose that the coalescence of crosslinked actin clusters could be key for sarcomeric pattern formation. In our simulations, sarcomere spacing is set by filament length prompting tight length control already at early stages of pattern formation. The proposed mechanism could be generic and apply both to premyofibrils and nascent myofibrils in developing muscle cells as well as possibly to striated stress-fibers in non-muscle cells.

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Actin cluster formation and coalescence.A. Our computational model of sarcomeric pattern formation considers a one-dimensional bundle of parallel actin filaments, which undergo treadmilling, i.e. filaments polymerize at their plus-ends and depolymerize at their minus-ends resulting in a net motion of the plus-end with respect to the individual monomers. Plus-end tracking crosslinkers (green) can permanently attach to the plus-ends of actin filaments (blue and red, indicating filament polarity), while still allowing for polymerization at filament plus-ends. B. Plus-end tracking crosslinking results in the formation and coalescence of actin clusters as reflected by a reduction in the number of actin clusters (single actin filaments are counted as one cluster). If there is no friction between sliding filaments (), all actin clusters eventually coalesce into a small number of very large clusters (blue, means.e., ). Time is measured in units of actin length divided by treadmilling speed, . In the presence of inter-filament friction (), however, actin clusters above a critical size effectively repel each other, resulting in a kinetically stabilized configuration with a finite number of actin clusters (magenta). To the right, example kymographs of actin cluster coalescence are shown for the cases without friction and with friction, respectively. A small imbalance in the number of filaments treadmilling either to the right or to the left within the final striated bundle causes a slow motion of the entire bundle as a whole as is reflected by the tilted cluster trajectories. Using static instead of periodic boundary conditions impedes this motion, see SI text S1. The color scheme encodes filament number in actin clusters as shown in the color bar.
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pcbi-1002544-g002: Actin cluster formation and coalescence.A. Our computational model of sarcomeric pattern formation considers a one-dimensional bundle of parallel actin filaments, which undergo treadmilling, i.e. filaments polymerize at their plus-ends and depolymerize at their minus-ends resulting in a net motion of the plus-end with respect to the individual monomers. Plus-end tracking crosslinkers (green) can permanently attach to the plus-ends of actin filaments (blue and red, indicating filament polarity), while still allowing for polymerization at filament plus-ends. B. Plus-end tracking crosslinking results in the formation and coalescence of actin clusters as reflected by a reduction in the number of actin clusters (single actin filaments are counted as one cluster). If there is no friction between sliding filaments (), all actin clusters eventually coalesce into a small number of very large clusters (blue, means.e., ). Time is measured in units of actin length divided by treadmilling speed, . In the presence of inter-filament friction (), however, actin clusters above a critical size effectively repel each other, resulting in a kinetically stabilized configuration with a finite number of actin clusters (magenta). To the right, example kymographs of actin cluster coalescence are shown for the cases without friction and with friction, respectively. A small imbalance in the number of filaments treadmilling either to the right or to the left within the final striated bundle causes a slow motion of the entire bundle as a whole as is reflected by the tilted cluster trajectories. Using static instead of periodic boundary conditions impedes this motion, see SI text S1. The color scheme encodes filament number in actin clusters as shown in the color bar.

Mentions: For simplicity, filaments are assumed to be rigid and incompressible with respective lengths , . For figures 2, 3, 4, filament lengths are monodisperse with for all ; whereas for figure 4 filament length are chosen from a log-normal distribution that satisfies and , see also the Supporting Information (SI).


Sarcomeric pattern formation by actin cluster coalescence.

Friedrich BM, Fischer-Friedrich E, Gov NS, Safran SA - PLoS Comput. Biol. (2012)

Actin cluster formation and coalescence.A. Our computational model of sarcomeric pattern formation considers a one-dimensional bundle of parallel actin filaments, which undergo treadmilling, i.e. filaments polymerize at their plus-ends and depolymerize at their minus-ends resulting in a net motion of the plus-end with respect to the individual monomers. Plus-end tracking crosslinkers (green) can permanently attach to the plus-ends of actin filaments (blue and red, indicating filament polarity), while still allowing for polymerization at filament plus-ends. B. Plus-end tracking crosslinking results in the formation and coalescence of actin clusters as reflected by a reduction in the number of actin clusters (single actin filaments are counted as one cluster). If there is no friction between sliding filaments (), all actin clusters eventually coalesce into a small number of very large clusters (blue, means.e., ). Time is measured in units of actin length divided by treadmilling speed, . In the presence of inter-filament friction (), however, actin clusters above a critical size effectively repel each other, resulting in a kinetically stabilized configuration with a finite number of actin clusters (magenta). To the right, example kymographs of actin cluster coalescence are shown for the cases without friction and with friction, respectively. A small imbalance in the number of filaments treadmilling either to the right or to the left within the final striated bundle causes a slow motion of the entire bundle as a whole as is reflected by the tilted cluster trajectories. Using static instead of periodic boundary conditions impedes this motion, see SI text S1. The color scheme encodes filament number in actin clusters as shown in the color bar.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369942&req=5

pcbi-1002544-g002: Actin cluster formation and coalescence.A. Our computational model of sarcomeric pattern formation considers a one-dimensional bundle of parallel actin filaments, which undergo treadmilling, i.e. filaments polymerize at their plus-ends and depolymerize at their minus-ends resulting in a net motion of the plus-end with respect to the individual monomers. Plus-end tracking crosslinkers (green) can permanently attach to the plus-ends of actin filaments (blue and red, indicating filament polarity), while still allowing for polymerization at filament plus-ends. B. Plus-end tracking crosslinking results in the formation and coalescence of actin clusters as reflected by a reduction in the number of actin clusters (single actin filaments are counted as one cluster). If there is no friction between sliding filaments (), all actin clusters eventually coalesce into a small number of very large clusters (blue, means.e., ). Time is measured in units of actin length divided by treadmilling speed, . In the presence of inter-filament friction (), however, actin clusters above a critical size effectively repel each other, resulting in a kinetically stabilized configuration with a finite number of actin clusters (magenta). To the right, example kymographs of actin cluster coalescence are shown for the cases without friction and with friction, respectively. A small imbalance in the number of filaments treadmilling either to the right or to the left within the final striated bundle causes a slow motion of the entire bundle as a whole as is reflected by the tilted cluster trajectories. Using static instead of periodic boundary conditions impedes this motion, see SI text S1. The color scheme encodes filament number in actin clusters as shown in the color bar.
Mentions: For simplicity, filaments are assumed to be rigid and incompressible with respective lengths , . For figures 2, 3, 4, filament lengths are monodisperse with for all ; whereas for figure 4 filament length are chosen from a log-normal distribution that satisfies and , see also the Supporting Information (SI).

Bottom Line: Using a one-dimensional computational model of an initially unstriated actin bundle, we show that actin filament treadmilling in the presence of processive plus-end crosslinking provides a simple and robust mechanism for the polarity sorting of actin filaments as well as for the correct localization of myosin filaments.In our simulations, sarcomere spacing is set by filament length prompting tight length control already at early stages of pattern formation.The proposed mechanism could be generic and apply both to premyofibrils and nascent myofibrils in developing muscle cells as well as possibly to striated stress-fibers in non-muscle cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot, Israel. ben@pks.mpg.de

ABSTRACT
Contractile function of striated muscle cells depends crucially on the almost crystalline order of actin and myosin filaments in myofibrils, but the physical mechanisms that lead to myofibril assembly remains ill-defined. Passive diffusive sorting of actin filaments into sarcomeric order is kinetically impossible, suggesting a pivotal role of active processes in sarcomeric pattern formation. Using a one-dimensional computational model of an initially unstriated actin bundle, we show that actin filament treadmilling in the presence of processive plus-end crosslinking provides a simple and robust mechanism for the polarity sorting of actin filaments as well as for the correct localization of myosin filaments. We propose that the coalescence of crosslinked actin clusters could be key for sarcomeric pattern formation. In our simulations, sarcomere spacing is set by filament length prompting tight length control already at early stages of pattern formation. The proposed mechanism could be generic and apply both to premyofibrils and nascent myofibrils in developing muscle cells as well as possibly to striated stress-fibers in non-muscle cells.

Show MeSH
Related in: MedlinePlus