A Perspective on the Role of Myosins as Mechanosensors

Abstract

Cells are dynamic systems that generate and respond to forces over a range of spatial and temporal scales, spanning from single molecules to tissues. Substantial progress has been made in recent years in identifying the molecules and pathways responsible for sensing and transducing mechanical signals to short-term cellular responses and longer-term changes in gene expression, cell identity, and tissue development. In this perspective article, we focus on myosin motors, as they not only function as the primary force generators in well-studied mechanobiological processes, but also act as key mechanosensors in diverse functions including intracellular transport, signaling, cell migration, muscle contraction, and sensory perception. We discuss how the biochemical and mechanical properties of different myosin isoforms are tuned to fulfill these roles in an array of cellular processes, and we highlight the underappreciated diversity of mechanosensing properties within the myosin superfamily. In particular, we use modeling and simulations to make predictions regarding how diversity in force sensing affects the lifetime of the actomyosin bond, the myosin power output, and the ability of myosin to respond to a perturbation in force for several nonprocessive myosin isoforms.

Modulating Beta-Cardiac Myosin Function at the Molecular and Tissue Levels

“…Thus, the following equation is often used to describe the maximum shortening velocity (Warshaw, 2004): $\begin{array}{c}left{\text{V}}_{\text{max}}={\text{d}}_{\text{uni}}/{\text{t}}_{\text{on}}\end{array}$ Since these parameters can be measured with isolated myosin, it is possible to correlate the individual properties of myosin with the contraction parameters in muscle. However, the t on is altered by the presence of load, as established in muscle fiber studies (Piazzesi et al, 2002; Reconditi et al, 2004) and further explored in single molecule mechanics studies (Sung et al, 2015; Greenberg et al, 2016). In addition, the factors that limit V max are controversial with some studies demonstrating detachment rate (1/t on ) correlates well with V max (Siemankowski et al, 1985; Nyitrai et al, 2006; Yengo et al, 2012) and other studies demonstrating attachment rate limits V max (Haldeman et al, 2014; Brizendine et al, 2015).…”

Stick-Slip Dynamics of Migrating Cells on Viscoelastic Substrates

“…The ligand-receptor bonds are modelled as Hookean springs of stiffness K c . As the F-actin bundle (modelled as a rigid rod), pulled by the myosin motors [9], moves with the retrograde velocity, v m , the spring gets stretched and thus, the force on a single bond is given by multiplying the spring stiffness with the bond elongation as,…”

“…During crawling, cell forms protrusions at the leading edge which pushes the membrane forward and as a consequence the membrane exerts a backward force on the polymerising actin filaments, resulting in them 'slipping' rearward towards the cell center, in a process known as retrograde flow [6][7][8]. This process is accompanied by growth and strengthening of focal adhesions between the cell and the substrate which slow down the actin retrograde flow [9]. Thus, it allows actin polymerization to advance at the leading edge and in turn, the rate of translocation of the cell increases [1,8,10,11].…”

Thermodynamic aspects of ATP hydrolysis of actomyosin complex

“…Moreover, each step that is associated with a large conformational change may contain a local transition state which determines the kinetics of the given step (Greenberg et al 2016). Such transition states (T-1–4) are presented schematically in Fig.…”