Bipolar filaments of human nonmuscle myosin 2-A and 2-B have distinct motile and mechanical properties

Abstract

Nonmuscle myosin 2 (NM-2) powers cell motility and tissue morphogenesis by assembling into bipolar filaments that interact with actin. Although the enzymatic properties of purified NM-2 motor fragments have been determined, the emergent properties of filament ensembles are unknown. Using single myosin filament in vitro motility assays, we report fundamental differences in filaments formed of different NM-2 motors. Filaments consisting of NM2-B moved processively along actin, while under identical conditions, NM2-A filaments did not. By more closely mimicking the physiological milieu, either by increasing solution viscosity or by copolymerization with NM2-B, NM2-A containing filaments moved processively. Our data demonstrate that both the kinetic and mechanical properties of these two myosins, in addition to the stochiometry of NM-2 subunits, can tune filament mechanical output. We propose altering NM-2 filament composition is a general cellular strategy for tailoring force production of filaments to specific functions such as maintaining tension or remodeling actin.

Actin bundle architecture and mechanics regulate myosin II force generation

“…Crosslinkers and other F-actin binding proteins could potentially dynamically tune local bundle mechanics, leading to spatial and temporal control of force generation. The different dependencies of myosin isoforms on mechanical feedback in building force (26,50) might cause bundle mechanics to shape the force response to different isoforms. We hypothesize that the isoform myosin IIa will be the most sensitive to bundle mechanics due to its force building mechanism.…”

Myosin-IIA heavy chain phosphorylation on S1943 regulates tumor metastasis

“…However, recent work suggests that when co-polymerized with myosin-IIB, or under high viscosity conditions that mimic the cytosol, myosin-IIA filaments move processively along F-actin [59]. Moreover, studies showing that ADP release from the myosin-IIA motor is only modestly affected by resistive loads suggest that this motor is more suited for rapid, short-lived contractile events such as moving cargo [60,61]. Increased myosin-IIA filament dynamics due to S1943 phosphorylation could therefore enhance vesicle trafficking.…”

Non-Muscle Myosin 2A (NM2A): Structure, Regulation and Function

“…Compared with NM2B, NM2A molecules have lower duty ratios, suggesting that NM2A homotypic filaments display a non-processive movement. Yet, NM2A/NM2B co-filaments move processively in vitro, on a viscous environment resembling the intracellular milieu, depending on the ratio of the two paralogs [ 59 ]. Whether NM2A can act as a processive myosin in vivo remains elusive.…”