Abstract
Recent experiments with super-resolution live cell microscopy revealed that nonmuscle myosin II minifilaments are much more dynamic than formerly appreciated, often showing plastic processes such as splitting, concatenation and stacking. Here we combine sequence information, electrostatics and elasticity theory to demonstrate that the parallel staggers at 14.3, 43.2 and 72 nm have a strong tendency to splay their heads away from the minifilament, thus potentially initiating the diverse processes seen in live cells. In contrast, the straight antiparallel stagger with an overlap of 43 nm is very stable and likely initiates minifilament nucleation. Using stochastic dynamics in a newly defined energy landscape, we predict that the optimal parallel staggers between the myosin rods are obtained by a trial-and-error process in which two rods attach and re-attach at different staggers by rolling and zipping motion. The experimentally observed staggers emerge as the configurations with the largest contact times. We find that contact times increase from isoforms C to B to A, that A-B-heterodimers are surprisingly stable and that myosin 18A should incorporate into mixed filaments with a small stagger. Our findings suggest that nonmuscle myosin II minifilaments in the cell are first formed by isoform A and then convert to mixed A-B-filaments, as observed experimentally.
Highlights
Myosin II is the most prominent subclass of the large myosin family of molecular motors that generate force and motion in the actin cytoskeleton [1]
Nonmuscle myosin II (NM2) is a non-processive molecular motor that assembles into minifilaments with a typical size of 300 nm to generate force and motion in the actin cytoskeleton
This process is essential for many cellular processes such as adhesion, migration, division and mechanosensing. Due to their small size below the resolution limit, minifilaments are a challenge for imaging with traditional light microscopy
Summary
Myosin II is the most prominent subclass of the large myosin family of molecular motors that generate force and motion in the actin cytoskeleton [1]. Considered to be the force generator in muscle cells, with the rise of mechanobiology it has become clear that myosin II is a central player in non-muscle cells [2]. It is involved in essential processes such as adhesion, migration and division, and in mechanosensing. Typically NM2A-minifilaments are formed at the front, become mixed A-B-filaments as they move towards the back, and are mainly B-filaments at the back Together, these recent observations lead to the central question how the molecular architecture of NM2-minifilaments, which formerly was assumed to be rather regular, can allow for such rich dynamics
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