Amplification of actin polymerization forces

763 The Rockefeller University Press $30.00 J. Cell Biol. Vol. 212 No. 7 763–766 www.jcb.org/cgi/doi/10.1083/jcb.201512019 Introduction Mechanical amplification is something we experience every day, in the form of gears, pulleys, and levers. While climbing a hill on a bicycle, for instance, shifting gears increases the force on the wheels while limiting the pressure required on the pedals. However, energy has to be conserved, and because mechanical work is defined as force × displacement, an increase in force can only be obtained at the expense of displacement. Thus, although shifting gears allows one to develop the additional force needed to go uphill, speed is reduced as each pedal stroke produces a smaller turn of the wheels. Cells have similarly developed microscopic force amplification strategies during evolution. Here, we discuss some amplification schemes for one of the major force generators in the cell—actin polymerization. Actin plays a ubiquitous role in cell motility and morphogenesis, spanning many scales of space and time. In fission yeast, for example, a miniature actin machinery only ∼100 nm across can induce the invagination of an endocytic vesicle in just a few seconds (Picco et al., 2015). However, to sever the entire yeast cell, a cytokinetic ring forms with an initial perimeter of ∼10 μm and requires ∼30 min to drive division (Proctor et al., 2012). These assemblies differ dramatically in both size and duration. In other species, considerably larger actin assemblies exist that reach the scale of centimeters, such as in muscle cells. Clearly, actin and its associated factors need to be specifically organized to achieve these different functions (Fig. 1). From a functional point of view, a key problem is to understand how the global architecture of an actin network allows forces that are produced at the molecular scale to be productive for the cell. In this respect, we can distinguish two sorts of components. Active components generate forces from chemical sources of energy and include molecular motors, as well as actin itself, which can push by polymerizing (Kovar and Pollard, 2004) and possibly pull while depolymerizing. Passive components, such as actin cross-linkers, are essential but can only transmit forces generated by other elements. The forces developed by an actin meshwork are determined by the organization of its components. Ultimately, these forces must be sufficient to drive biological processes, and thus their scale depends on the physical characteristics of the cell. For example, in the case of endocytosis in yeast, the turgor pressure pushing the surface of the invagination outward reaches ∼1,000 pN, which the actin machinery must overcome (Basu et al., 2014). During cytokinesis, the actomyosin ring also works against the turgor pressure, which produces high forces on the furrow (Proctor et al., 2012). For both cases, these forces have been calculated from measured cellular parameters, particularly the turgor pressure and the dimensions over which the membrane is deformed. Hence, for these processes at least, the two ends of the problem are known: the forces produced by the molecular components make up the input and the force required for the cellular process to occur represents the output. Yet the force balance within the system must be considered to understand how the actin machinery harvests the input to produce this output. In this comment, we focus on the transmission of forces produced by the polymerization of actin, setting aside turnover and the contribution of molecular motors. We discuss specifically how the arrangement of the filaments in the system regulates the amount of productive force. In many ways, the actin machinery behaves analogously to a cyclist: though its power is limited, it can “shift gears” to favor either more displacement (high gears) or more force (low gears).