Mechanical signaling in networks of motor and cytoskeletal proteins.

The motions of cells and organelles are highly coordinated. They are driven by motor proteins moving along cytoskeletal filaments, and by the dynamic growth and shrinkage of the filaments themselves. The initiation of cellular motility is triggered by biochemical signaling pathways, but the coordination of motility at different locations or times is not well understood. In this review I discuss a new hypothesis that motility is coordinated through mechanical signals passing between and regulating the activity of motors and filaments. The signals are carried by forces and sensed through the acceleration of protein-protein dissociation rates. Mechanical signaling can lead to spontaneous symmetry breaking, switching, and oscillations, and it can account for a wide range of cell motions such as the flagellar beat, mitotic spindle movements, and bidirectional organelle transport. Because forces can propagate quickly, mechanical signaling is ideal for coordinating motion over large distances.

[1]  Anthony A. Hyman,et al.  Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner , 2006, Nature Cell Biology.

[2]  H. Sweeney,et al.  The Structural Basis for the Large Powerstroke of Myosin VI , 2007, Cell.

[3]  W. Marshall.  Cellular length control systems. , 2004, Annual review of cell and developmental biology.

[4]  Hideo Higuchi,et al.  Overlapping hand-over-hand mechanism of single molecular motility of cytoplasmic dynein. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Samara L. Reck-Peterson,et al.  Force-Induced Bidirectional Stepping of Cytoplasmic Dynein , 2007, Cell.

[6]  Anthony A. Hyman,et al.  Spindle Oscillations during Asymmetric Cell Division Require a Threshold Number of Active Cortical Force Generators , 2006, Current Biology.

[7]  E. Salmon,et al.  The spindle-assembly checkpoint in space and time , 2007, Nature Reviews Molecular Cell Biology.

[8]  J. Howard,et al.  Elastic and damping forces generated by confined arrays of dynamic microtubules , 2006, Physical biology.

[9]  L. Addadi,et al.  Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates , 2001, Nature Cell Biology.

[10]  E. Mandelkow,et al.  The structure of microtubule motor proteins. , 2005, Advances in protein chemistry.

[11]  E. Achenbach,et al.  Experiments on the flow past spheres at very high Reynolds numbers , 1972, Journal of Fluid Mechanics.

[12]  Prost,et al.  Cooperative molecular motors. , 1995, Physical review letters.

[13]  B. Hille,et al.  External Ca2+ acts upstream of adenylyl cyclase SACY in the bicarbonate signaled activation of sperm motility. , 2007, Developmental biology.

[14]  F. Jülicher,et al.  Bidirectional cooperative motion of molecular motors , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. McIntosh,et al.  The Molecular Architecture of Axonemes Revealed by Cryoelectron Tomography , 2006, Science.

[16]  R. Cross,et al.  Mechanics of the kinesin step , 2005, Nature.

[17]  P. Iglesias,et al.  A Mechanosensory System Controls Cell Shape Changes During Mitosis , 2007, Cell cycle.

[18]  Manuel Théry,et al.  Experimental and theoretical study of mitotic spindle orientation , 2007, Nature.

[19]  G. C. Rogers,et al.  Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase , 2004, Nature.

[20]  F. Jülicher,et al.  Generic aspects of axonemal beating , 2000 .

[21]  F. Jülicher,et al.  The chirality of ciliary beats , 2008, Physical biology.

[22]  William Hyde Wollaston,et al.  I. The Croonian Lecture , 1810, Philosophical Transactions of the Royal Society of London.

[23]  Donald E Ingber,et al.  Mechanical control of tissue morphogenesis during embryological development. , 2006, The International journal of developmental biology.

[24]  Paul R. Selvin,et al.  Single-molecule techniques , 2008 .

[25]  Anthony A. Hyman,et al.  Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo , 2001, Nature.

[26]  J. Labbé,et al.  Heterotrimeric G protein signaling functions with dynein to promote spindle positioning in C. elegans , 2007, The Journal of cell biology.

[27]  Jonathon Howard,et al.  The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends , 2006, Nature.

[28]  Daniel J. Muller,et al.  Single-cell force spectroscopy , 2008, Journal of Cell Science.

[29]  E. Evans.  Probing the relation between force--lifetime--and chemistry in single molecular bonds. , 2001, Annual review of biophysics and biomolecular structure.

[30]  Marileen Dogterom,et al.  Force generation by dynamic microtubules. , 2005, Current opinion in cell biology.

[31]  Katherine C. Chen,et al.  Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. , 2003, Current opinion in cell biology.

[32]  M. Schnitzer,et al.  Force production by single kinesin motors , 2000, Nature Cell Biology.

[33]  S. Grillner,et al.  Neural networks for vertebrate locomotion. , 1996, Scientific American.

[34]  J. Prost,et al.  Spontaneous Oscillations of Collective Molecular Motors , 1996, cond-mat/9611204.

[35]  M. Fisher,et al.  Mechanoenzymes under superstall and large assisting loads reveal structural features , 2007, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Steven H. Strogatz,et al.  Nonlinear Dynamics and Chaos , 2024 .

[37]  M. Sheetz,et al.  Local force and geometry sensing regulate cell functions , 2006, Nature Reviews Molecular Cell Biology.

[38]  Jonathon Howard,et al.  The Distribution of Active Force Generators Controls Mitotic Spindle Position , 2003, Science.

[39]  Frank Jülicher,et al.  Theory of mitotic spindle oscillations. , 2005, Physical review letters.

[40]  S. Ishiwata,et al.  Auto-oscillations of Skinned Myocardium Correlating with Heartbeat , 2005, Journal of Muscle Research & Cell Motility.

[41]  Stefan Westermann,et al.  The Dam1 kinetochore ring complex moves processively on depolymerizing microtubule ends , 2006, Nature.

[42]  J. Pringle.  The Croonian Lecture, 1977 - Stretch activation of muscle: function and mechanism , 1978, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[43]  Julie A. Theriot,et al.  Mechanism of shape determination in motile cells , 2008, Nature.

[44]  J. Howard,et al.  Mechanics of Motor Proteins and the Cytoskeleton , 2001 .

[45]  G. Borisy,et al.  Self-centring activity of cytoplasm , 1997, Nature.

[46]  I. Tolic-Nørrelykke.  Push-me-pull-you: how microtubules organize the cell interior , 2008, European Biophysics Journal.

[47]  C. Brokaw.  Molecular mechanism for oscillation in flagella and muscle. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[48]  M. Carlier,et al.  Regulation of actin assembly associated with protrusion and adhesion in cell migration. , 2008, Physiological reviews.

[49]  Pasko Rakic,et al.  Mitotic spindle rotation and mode of cell division in the developing telencephalon , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[50]  S. E. Khaikin,et al.  Theory of Oscillators , 1966 .

[51]  Alan Hall,et al.  Rho GTPases: biochemistry and biology. , 2005, Annual review of cell and developmental biology.

[52]  J. J. Hopfield,et al.  “Neural” computation of decisions in optimization problems , 1985, Biological Cybernetics.

[53]  A. Hodgkin,et al.  Temporal and spatial characteristics of the voltage response of rods in the retina of the snapping turtle , 1980, The Journal of physiology.

[54]  Melanie J. I. Müller,et al.  Tug-of-war as a cooperative mechanism for bidirectional cargo transport by molecular motors , 2008, Proceedings of the National Academy of Sciences.

[55]  Uri Alon,et al.  An Introduction to Systems Biology , 2006 .

[56]  Jasper van der Gucht,et al.  Cracking up: symmetry breaking in cellular systems , 2006, The Journal of cell biology.

[57]  Ingmar H. Riedel-Kruse,et al.  How Molecular Motors Shape The Flagellar Beat , 2009 .

[58]  Frank Jülicher,et al.  Unifying the various incarnations of active hair-bundle motility by the vertebrate hair cell. , 2007, Biophysical journal.

[59]  T. Pollard,et al.  Insertional assembly of actin filament barbed ends in association with formins produces piconewton forces. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[60]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[61]  Cleopatra Kozlowski,et al.  Cortical Microtubule Contacts Position the Spindle in C. elegans Embryos , 2007, Cell.

[62]  U. Kaupp,et al.  Mechanisms of sperm chemotaxis. , 2008, Annual review of physiology.

[63]  Trisha N Davis,et al.  The Dam1 kinetochore complex harnesses microtubule dynamics to produce force and movement. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[64]  Matthias Rief,et al.  Force-dependent stepping kinetics of myosin-V. , 2005, Biophysical journal.

[65]  L. Lanzetti,et al.  Actin in membrane trafficking. , 2007, Current opinion in cell biology.

[66]  M. Welte,et al.  Bidirectional Transport along Microtubules , 2004, Current Biology.