Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jan 18;102(2):238-47.
doi: 10.1016/j.bpj.2011.12.020.

Understanding the cooperative interaction between myosin II and actin cross-linkers mediated by actin filaments during mechanosensation

Tianzhi Luo  1 , Krithika Mohan, Vasudha Srivastava, Yixin Ren, Pablo A Iglesias, Douglas N Robinson
Affiliations

Understanding the cooperative interaction between myosin II and actin cross-linkers mediated by actin filaments during mechanosensation

Tianzhi Luo et al. Biophys J. .

Abstract

Myosin II is a central mechanoenzyme in a wide range of cellular morphogenic processes. Its cellular localization is dependent not only on signal transduction pathways, but also on mechanical stress. We suggest that this stress-dependent distribution is the result of both the force-dependent binding to actin filaments and cooperative interactions between bound myosin heads. By assuming that the binding of myosin heads induces and/or stabilizes local conformational changes in the actin filaments that enhances myosin II binding locally, we successfully simulate the cooperative binding of myosin to actin observed experimentally. In addition, we can interpret the cooperative interactions between myosin and actin cross-linking proteins observed in cellular mechanosensation, provided that a similar mechanism operates among different proteins. Finally, we present a model that couples cooperative interactions to the assembly dynamics of myosin bipolar thick filaments and that accounts for the transient behaviors of the myosin II accumulation during mechanosensation. This mechanism is likely to be general for a range of myosin II-dependent cellular mechanosensory processes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Dimer addition model for myosin BTF assembly in the presence of actin filaments. M, D, and T represent the monomer (the hexameric monomer with two heavy chains, two essential light chains, and two regulatory light chains), dimer, and tetramer, respectively, BTF3, BTFn, and BTFn+1 are the bipolar filaments having 6, 2n, and 2(n+1) monomers, respectively, and n is the number of dimers. The superscripts (∗) and bar (−) represent the actin-bound state and the incompetent forms, respectively. The rate constant k1 = konCactin, where kon is the on-rate for myosin binding to actin and Cactin is the F-actin concentration; k− can be determined by the BTF concentration at steady state. The value k−1 is a function of the concentration of myosin (m) and/or applied force (m, F).
Figure 2
Figure 2
Mechanosensitive accumulation of myosin II and cortexillin I. (A) The transient curves of the accumulation of myosin II and cortexillin I of a single wild-type cell. (Asterisk in the graph) Point where the inset was derived. (Inset) Spatial pattern of GFP-myosin II accumulation during mechanosensing. (Open arrow) Tip position inside the micropipette. (B) The normalized myosin II accumulation magnitude increases overtime at different pressures. (Scattered symbols) Experimental data and lines show the trend. (C) The corresponding accumulation rates calculated from the data in panel B with initial cortical myosin concentration of 4.2 μM (17).
Figure 3
Figure 3
Simulation results of homocooperative binding of myosin II to the actin filaments. (A) Coverage of actin filaments by bound myosins, ϕ (i.e., the fraction of myosin binding sites on actin occupied by myosin) as a function of initial myosin concentrations at different strain energies. (B) A representative snapshot of myosin clusters (aligned bright dots) on the actin filaments. (Scattered shaded dots) Freely diffusing monomers. (C) The cluster size increases with Es0 in the cases where the total number of myosin is either 0.05 N2 (open squares) or 0.1 N2 (open circles). (D) The fraction of bound myosin increases with increasing strain energy, Es0. The simulation window size was N = 128.
Figure 4
Figure 4
Simulation results of heterocooperative binding of myosin II and cortexillin I to the actin filaments. (A) A representative snapshot of the clusters formed by myosin and cortexillin due to heterocooperativity. (Yellow and red dots) Bound myosins and cortexillins, respectively; (gray and green dots) unbound myosins and cortexillins, respectively. (B) The fraction of bound proteins at steady state increases as a function of strain energy, Es0.
Figure 5
Figure 5
BTF assembly and myosin accumulation for different applied forces. The simulated myosin accumulation and accumulation rate for different Fd values are shown in panels A and B, respectively. Simulations for Fd = 0 and 120 kBT (solid lines) are compared to experimental observations (scattered symbols) at pressure of 0.2 and 1.0 nN/μm2 in panels C and D, respectively. For all simulated cases, k1 = 14 s−1 and Es0 = 3 kBT (see the Supporting Material for the Fd to pressure conversion). Data from six cells at each pressure are provided to illustrate the range of cellular responses. Experimental and simulation data were aligned at the peak intensities.
Figure 6
Figure 6
Spatial distribution of myosin BTFs in a mechanosensory response. (A) Cartoon diagram of myosin transport due to the spatial bias of force. (B) Spatial concentration of myosin at 200 s, calculated by solving the three-dimensional reaction-diffusion equations for WT myosin II and 3×Ala myosin II mutant. The associated movies for these two-dimensional simulations may be found in Movie S3 and Movie S4 in the Supporting Material. For comparison, a movie (see Movie S5) from a three-dimensional simulation is provided, which showed very similar results. (C) The myosin accumulation increased with the applied force on each myosin head (see Fig. S11 in the Supporting Material for an alternative representation).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Spudich J.A. The myosin swinging cross-bridge model. Nat. Rev. Mol. Cell Biol. 2001;2:387–392. - PubMed
    1. Effler J.C., Kee Y.-S., et al. Robinson D.N. Mitosis-specific mechanosensing and contractile protein redistribution control cell shape. Curr. Biol. 2006;16:1962–1967. - PMC - PubMed
    1. Ren Y., Effler J.C., et al. Robinson D.N. Mechanosensing through cooperative interactions between myosin II and the actin crosslinker cortexillin I. Curr. Biol. 2009;19:1421–1428. - PMC - PubMed
    1. Wozniak M.A., Chen C.S. Mechanotransduction in development: a growing role for contractility. Nat. Rev. Mol. Cell Biol. 2009;10:34–43. - PMC - PubMed
    1. Greene L.E., Eisenberg E. Cooperative binding of myosin subfragment-1 to the actin-troponin-tropomyosin complex. Proc. Natl. Acad. Sci. USA. 1980;77:2616–2620. - PMC - PubMed

Publication types

LinkOut - more resources