It is intriguing how the mechanics of molecular motors is regulated to perform the mechanical work in living systems. In sharp contrast to the conventional wisdom, recent experiments indicated that motor force maintains ∼6 pN upon a wide range of filament loads during skeletal muscle contraction at the steady state. Here we find that this rather precise regulation which takes place in an essentially chaotic system, can be due to that a “working” motor is arrested in a transitional state when the motor force is ∼6 pN. Our analysis suggests that the motor force can be self-regulated through chemomechanical coupling, and motor force homeostasis is a built-in feature at the level of a single motor, which provides insights to understanding the coordinated function of multiple molecular motors existing in various physiological processes. With a coupled stochastic-elastic numerical framework, the kinetic model for a Actin-myosin-ATP cycle constructed in this work might pave the way to decently investigate the transient behaviors of the skeletal muscle or other actomyosin complex structures.

References

1.
Huxley
,
A. F.
,
1957
, “
Muscle Structure and Theories of Contraction
,”
Prog. Biophys. Biophys. Chem.
,
7
, pp.
255
318
.
2.
Cooke
,
R
.,
1997
, “
Actomyosin Interaction in Striated Muscle
,”
Physiol. Rev.
,
77
, pp.
671
697
.
3.
Piazzesi
,
G.
,
Reconditi
,
M.
,
Linari
,
M.
,
Lucii
,
L.
,
Bianco
,
P.
,
Brunello
,
E.
,
Decostre
,
V.
,
Stewart
,
A.
,
Gore
,
D. B.
,
Irving
,
T. C.
,
Irving
,
M.
, and
Lombardi
,
V.
,
2007
, “
Skeletal Muscle Performance Determined by Modulation of Number of Myosin Motors Rather Than Motor Force or Stroke Size
,”
Cell
,
131
, pp.
784
795
.10.1016/j.cell.2007.09.045
4.
Duke
,
T. A.
,
1999
, “
Molecular Model of Muscle Contraction
,”
Proc. Natl. Acad. Sci. U. S. A.
,
96
, pp.
2770
2775
.10.1073/pnas.96.6.2770
5.
Chen
,
B.
, and
Gao
,
H.
,
2011
, “
Motor Force Homeostasis in Skeletal Muscle Contraction
,”
Biophys J.
,
101
, pp.
396
403
.10.1016/j.bpj.2011.05.061
6.
Guo
,
B.
, and
Guilford
,
W. H.
,
2006
, “
Mechanics of Actomyosin Bonds in Different Nucleotide States are Tuned to Muscle Contraction
,”
Proc. Natl. Acad. Sci. U. S. A.
,
103
, pp.
9844
9849
.10.1073/pnas.0601255103
7.
Huxley
,
A. F.
, and
Simmons
,
R. M.
,
1971
, “
Proposed Mechanism of Force Generation in Striated Muscle
,”
Nature
,
233
, pp.
533
538
.10.1038/233533a0
8.
Ford
,
L. E.
,
Huxley
,
A. F.
, and
Simmons
,
R. M.
,
1977
, “
Tension Responses to Sudden Length Change in Stimulated Frog Muscle Fibres Near Slack Length
,”
J. Physiol.
,
269
, pp.
441
515
.
9.
Piazzesi
,
G.
, and
Lombardi
,
V.
,
1995
, “
A Cross-Bridge Model That is Able to Explain Mechanical and Energetic Properties of Shortening Muscle
,”
Biophys. J.
,
68
, pp.
1966
1979
.10.1016/S0006-3495(95)80374-7
10.
Hill
,
A. V.
,
1938
, “
The Heat of Shortening, and Dynamics Constants of Muscle
,”
Proc. R. Soc. Lond. Ser. B
,
126
, pp.
136
195
.10.1098/rspb.1938.0050
11.
Lymn
,
R. W.
, and
Taylor.
,
E. W.
,
1971
, “
Mechanism of Adenosine Triphosphate Hydrolysis by Actomyosin
,”
Biochemistry
,
10
, pp.
4617
4624
.10.1021/bi00801a004
12.
Fortune
,
N. S.
,
Geeves
,
M. A.
, and
Ranatunga
,
K. W.
,
1991
, “
Tension Responses to Rapid Pressure Release in Glycerinated Rabbit Muscle Fibers
,”
Proc. Natl. Acad. Sci. USA
,
88
, pp.
7323
7327
.10.1073/pnas.88.16.7323
13.
Dantzig
,
J. A.
,
Goldman
,
Y. E.
,
Millar
,
N. C.
,
Lacktis
,
J.
, and
Homsher
,
E.
,
1992
, “
Reversal of the Cross-Bridge Force-Generating Transition by Photogeneration of Phosphate in Rabbit Psoas Muscle Fibres
,”
J. Physiol.
,
451
, pp.
247
278
.
14.
Kawai
,
M.
, and
Halvorson
,
H. R.
,
1991
, “
Two Step Mechanism of Phosphate Release and the Mechanism of Force Generation in Chemically Skinned Fibers of Rabbit Psoas Muscle
,”
Biophys. J.
,
59
, pp.
329
342
.10.1016/S0006-3495(91)82227-5
15.
Geeves
,
M. A.
, and
Holmes
,
K. C.
,
1999
, “
Structural Mechanism of Muscle Contraction
,”
Ann. Rev. Biochem.
,
68
, pp.
687
728
.10.1146/annurev.biochem.68.1.687
16.
Cooke
,
R
.,
1986
, “
The Mechanism of Muscle Contraction
,”
CRC Crit. Rev. Biochem.
,
21
, pp.
53
118
.10.3109/10409238609113609
17.
Berger
,
C. E.
,
Fagnant
,
P. M.
,
Heizmann
,
S.
,
Trybus
,
K. M.
, and
Geeves
,
M. A.
,
2001
, “
ADP Binding Induces an Asymmetry Between the Heads of Unphosphorylated Myosin
,”
J. Biol. Chem.
,
276
, pp.
23240
23245
.10.1074/jbc.M100524200
18.
Nyitrai
,
M.
, and
Geeves
,
M. A.
,
2004
, “
Adenosine Diphosphate and Strain Sensitivity in Myosin Motors
,”
Philos. Trans. R. Soc. London, Ser. B
,
359
, pp.
1867
1877
.10.1098/rstb.2004.1560
19.
Bloemink
,
M. J.
,
Adamek
,
N.
,
Reggiani
,
C.
, and
Geeves
,
M. A.
,
2007
, “
Kinetic Analysis of the Slow Skeletal Myosin MHC-1 Isoform From Bovine Masseter Muscle
,”
J. Mol. Biol.
,
373
, pp.
1184
1197
.10.1016/j.jmb.2007.08.050
20.
Smith
,
D. A.
, and
Geeves
,
M. A.
,
1995
, “
Strain-Dependent Cross-Bridge Cycle for Muscle
,”
Biophys. J.
,
69
, pp.
524
537
.10.1016/S0006-3495(95)79926-X
21.
Duke
,
T
.,
2000
, “
Cooperativity of Myosin Molecules Through Strain-Dependent Chemistry
,”
Philos. Trans. R. Soc. London, Ser. B
,
355
, pp.
529
538
.10.1098/rstb.2000.0594
22.
Veigel
,
C.
,
Molloy
,
J. E.
,
Schmitz
,
S.
, and
Kendrick-Jones
,
J.
,
2003
, “
Load-Dependent Kinetics of Force Production by Smooth Muscle Myosin Measured With Optical Tweezers
,”
Nat. Cell Biol.
,
5
, pp.
980
986
.10.1038/ncb1060
23.
Veigel
,
C.
,
Coluccio
,
L. M.
,
Jontes
,
J. D.
,
Sparrow
,
J. C.
,
Milligan
,
R. A.
, and
Molloy
,
J. E.
,
1999
, “
The Motor Protein Myosin-I Produces Its Working Stroke in Two Steps
,”
Nature
,
398
, pp.
530
533
.10.1038/19104
24.
Bell
,
G. I.
,
1978
, “
Models for the Specific Adhesion of Cells to Cells
,”
Science
,
200
, pp.
618
627
.10.1126/science.347575
25.
Piazzesi
,
G.
,
Reconditi
,
M.
, and
Lombardi
,
V.
,
2003
, “
Temperature Dependence of the Force-Generating Process in Single Fibers From Frog Skeletal Muscle
,”
J. Physiol.
,
549
, pp.
93
106
.10.1113/jphysiol.2002.038703
26.
Decostre
,
V.
,
Bianco
,
P.
, and
Piazzesi
,
G.
,
2005
, “
Effect of Temperature on the Working Stroke of Muscle Myosin
,”
Proc. Natl. Acad. Sci. USA
,
102
, pp.
13927
13932
.10.1073/pnas.0506795102
27.
Linari
,
M.
,
Brunello
,
E.
, and
Irving
,
M.
,
2005
, “
The Structural Basis of the Increase in Isometric Force Production With Temperature in Frog Skeletal Muscle
,”
J. Physiol.
,
567
, pp.
459
469
.10.1113/jphysiol.2005.089672
28.
Capitanio
,
M.
,
Canepari
,
M.
,
Cacciafesta
,
P.
,
Lombardi
,
V.
,
Cicchi
,
R.
,
Maffei
,
M.
,
Pavone
,
E. S.
, and
Bottinelli
,
R.
,
2006
, “
Two Independent Mechanical Events in the Interaction Cycle of Skeletal Muscle Myosin With Actin
,”
Proc. Natl. Acad. Sci. USA
,
103
, pp.
87
92
.10.1073/pnas.0506830102
29.
Eriksen
,
R. L.
,
Daria
,
V. R.
, and
Gluckstad
,
J.
,
2002
, “
Fully Dynamic Multiple-Beam Optical Tweezers
,”
Opt. Express
,
10
(
14
), pp.
597
602
.10.1364/OE.10.000597
30.
Bao
,
G
.,
2002
, “
Mechanics of Biomolecules
,”
J. Mech. Phys. Solids.
,
50
, pp.
2237
2274
.10.1016/S0022-5096(02)00035-2
You do not currently have access to this content.