Myosin-driven fragmentation of actin filaments triggers contraction of a disordered actin network
The dynamic cytoskeletal network is responsible for cell shape changes and cell division. The actin-based motor protein myosin II drives the remodeling of a highly disordered actin-based network and enables the network to perform mechanical work such as contraction, migration and adhesion. Myosin II forms bipolar filaments that self-associate via their tail domains. Such myosin minifilaments generate both extensile and compressive forces that pull and push actin filaments, depending on the relative position of myosin and actin filaments in the network. However, it remains unclear how the mechanical properties of myosin II that rely on the energy of ATP hydrolysis spontaneously contract the disordered actin network. Here, we used a minimal in vitro reconstituted experimental system consisting of actin, myosin, and a cross-linking protein, to gain insights into the molecular mechanism by which myosin minifilaments organize disordered actin networks into contractile states. We found that contracted cluster size and time required for the onset of network contraction decreased as ATP concentration decreased. Contraction velocity was negatively correlated with ATP concentrations. Reduction of ATP concentration caused fragmentation of actin filaments by myosin minifilament. We also found that gelsolin, a Ca2+-regulated actin filament-severing protein, induced contraction of a mechanically stable network, implying that fragmentations of actin filaments in the network weaken the intra-network connectivity and trigger contraction. Our findings reveal that the disordered actin network contraction can be controlled by fragmentation of actin filaments, highlighting the molecular mechanism underlying the myosin motor-severing activities, other than the sliding tensile and compressive stress in the disordered actin network.