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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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Myosin order despite actin turnover.We devised a minimal model of actin filament turnover, see main text. For simulations as in figure 3, but with actin turnover, the sarcomeric order parameter was found to decrease as a function of actin filament turnover rate (blue curve) as actin turnover impedes the formation of large actin clusters (blue, means.e., ). Surprisingly, an analogously defined order parameter for myosin positions attains significant values even for considerable actin turnover rates. A simulation snap-shot at  is shown to the right for actin turnover rate  (in units of ).
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pcbi-1002544-g005: Myosin order despite actin turnover.We devised a minimal model of actin filament turnover, see main text. For simulations as in figure 3, but with actin turnover, the sarcomeric order parameter was found to decrease as a function of actin filament turnover rate (blue curve) as actin turnover impedes the formation of large actin clusters (blue, means.e., ). Surprisingly, an analogously defined order parameter for myosin positions attains significant values even for considerable actin turnover rates. A simulation snap-shot at is shown to the right for actin turnover rate (in units of ).

Mentions: Actin filament length control and turnover of filaments both depend crucially on the polymerization and depolymerization dynamics of actin filaments. Thus, length control and filament turnover are in principle inseparable. This being said, we nonetheless aimed at isolating the qualitative effect of actin turnover. To this end, we augmented our computational model by including prototypical actin dynamics that differentiates between idealized dynamic regimes of either (i) steady-state treadmilling with constant actin filament length , (ii) ‘actin catastrophies’ characterized by fast and complete depolymerization of filaments that occur with rate , and (iii) rapid de novo polymerization of new actin filaments [46]. These simple limits are not intended to realistically depict actin dynamics. Rather they allow us to study the qualitative effects of actin filament turnover, without changing the filament length distribution. As expected, actin filament turnover interferes with the formation of large actin clusters and results in reduced sarcomeric order, see figure 5. Surprisingly, myosin is still sorted into regular A-bands even for considerable actin turnover rates. We conclude that partial polarity sorting of actin filaments is sufficient to sort myosin into A-bands. This may provide an explanation for experimental observations in which myosin ordering was observed to precede the formation of large, periodically spaced I-Z-I complexes.


Sarcomeric pattern formation by actin cluster coalescence.

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

Myosin order despite actin turnover.We devised a minimal model of actin filament turnover, see main text. For simulations as in figure 3, but with actin turnover, the sarcomeric order parameter was found to decrease as a function of actin filament turnover rate (blue curve) as actin turnover impedes the formation of large actin clusters (blue, means.e., ). Surprisingly, an analogously defined order parameter for myosin positions attains significant values even for considerable actin turnover rates. A simulation snap-shot at  is shown to the right for actin turnover rate  (in units of ).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002544-g005: Myosin order despite actin turnover.We devised a minimal model of actin filament turnover, see main text. For simulations as in figure 3, but with actin turnover, the sarcomeric order parameter was found to decrease as a function of actin filament turnover rate (blue curve) as actin turnover impedes the formation of large actin clusters (blue, means.e., ). Surprisingly, an analogously defined order parameter for myosin positions attains significant values even for considerable actin turnover rates. A simulation snap-shot at is shown to the right for actin turnover rate (in units of ).
Mentions: Actin filament length control and turnover of filaments both depend crucially on the polymerization and depolymerization dynamics of actin filaments. Thus, length control and filament turnover are in principle inseparable. This being said, we nonetheless aimed at isolating the qualitative effect of actin turnover. To this end, we augmented our computational model by including prototypical actin dynamics that differentiates between idealized dynamic regimes of either (i) steady-state treadmilling with constant actin filament length , (ii) ‘actin catastrophies’ characterized by fast and complete depolymerization of filaments that occur with rate , and (iii) rapid de novo polymerization of new actin filaments [46]. These simple limits are not intended to realistically depict actin dynamics. Rather they allow us to study the qualitative effects of actin filament turnover, without changing the filament length distribution. As expected, actin filament turnover interferes with the formation of large actin clusters and results in reduced sarcomeric order, see figure 5. Surprisingly, myosin is still sorted into regular A-bands even for considerable actin turnover rates. We conclude that partial polarity sorting of actin filaments is sufficient to sort myosin into A-bands. This may provide an explanation for experimental observations in which myosin ordering was observed to precede the formation of large, periodically spaced I-Z-I complexes.

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