INSTITUTE OF PHYSICS PUBLISHING PHYSICAL BIOLOGYPhys. Biol. 1 (2004) T1–T10 PII: S1478-3967(04)70333-2TUTORIALAn introduction to cell motility for thephysical scientistDaniel A Fletcher1and Julie A Theriot21Department of Bioengineering and Biophysics Program, University of California at Berkeley, Berkeley,CA 94720, USA2Departments of Biochemistry and of Microbiology and Immunology, Stanford University School ofMedicine, Stanford, CA 94305, USAReceived 10 October 2003Accepted for publication 11 December 2003Published 12 February 2004Online at stacks.iop.org/PhysBio/1/T1 (DOI: 10.1088/1478-3967/1/1/T01)AbstractDirected, purposeful movement is one of the qualities that we most closely associate withliving organisms, and essentially all known forms of life on this planet exhibit some type ofself-generated movement or motility. Even organisms that remain sessile most of the time, likeflowering plants and trees, are quite busy at the cellular level, with large organelles, includingchloroplasts, constantly racing around within cellular boundaries. Directed biologicalmovement requires that the cell be able to convert its abundant stores of chemical energy intomechanical energy. Understanding how this mechanochemical energy transduction takes placeand understanding how small biological forces generated at the molecular level are marshaledand organized for large-scale cellular or organismal movements are the focus of the field ofcell motility. This tutorial, aimed at readers with a background in physical sciences, surveysthe state of current knowledge and recent advances in modeling cell motility.Preface‘I can remember the scene vividly—a fish epithelial cell knownas a keratocyte moving in slow motion across the microscope’sfield of view. After plucking a scale from a goldfish and lettingit incubate in media overnight, I was watching a doggedlydetermined, self-contained protein machine crawl across theslide. Amazing. I’d had years of training in engineeringand physical science, and nothing we know how to buildhas that much functionality in such a small package. Howdoes this cell move? How is it controlled? What is itsrole in preserving health? Most students of cell biologyarrive at these questions as undergraduates or earlier, but ittook me a little longer. After several degrees investigatingand manipulating inanimate materials, I was attempting tolearn basic biology as a postdoc. The process had itsshare of frustrations—experimental uncertainties, cell-to-cellvariability, different sets of assumptions—but the eleganceand robustness of biological systems never cease to amazeme. Exciting opportunities await those willing to embrace thechallenge of learning a new field and applying the experimentaland analytical tools of physical science to biological questions.Quantitative biology is alive and growing, and the potentialimpacts on health, disease, and technology are enormous.There is no time like the present to peer into the microscopeand see what’s crawling by.’—DAF1. Biological and physical importance of cellmovementsProblems in the movement of cells and their internalcomponents are the topic of a great deal of investigation,because of the intrinsic interest of the processes and becauseof their medical importance [1]. Most cancers are not life-threatening until they metastasize and spread throughout thebody. Metastasis occurs when previously sessile cells in atumor acquire the ability to move and invade nearby tissuesand circulate in the bloodstream or lymphatic system. Atreatment that blocked the ability of tumor cells to acquiremotility would largely prevent metastasis. The elaboratewiring of the human nervous system is generated during fetal1478-3967/04/010001+10$30.00 © 2004 IOP Publishing Ltd Printed in the UK T1TutorialTable 1. Cell movements and their molecular mechanisms.Cell movement Cell structure needed Molecular motor Motor categoryMovements through liquidBacterial swimming Flagella (bacterial) Flagellar rotor (MotA/MotB) RotaryEukaryotic swimming Cilia, flagella (eukaryotic) Dynein Linear stepperMetaboly Unknown Unknown UnknownMovements on solid surfacesAmoeboid motility (crawling) Lamellipodia, filopodia, pseudopodia Actin Assembly/disassemblyMyosin (several) Linear stepperBacterial gliding Junctional pore complex Slime extrusion nozzle ExtrusionParasite gliding Pellicle Myosin (class XIV) Linear stepper (probably)Bacterial twitching Type IV pili Pilus base motor (PilT) Assembly/disassembly?Linear Stepper?Intracellular movementsChromosome segregation Mitotic spindle Kinesin (several), dynein Linear stepperTubulin Assembly/disassemblyOrganelle transport Microtubule arrays Kinesin (several), dynein Linear stepperActin gels Myosin (class V, class VI, others?) Linear stepperActin comets Actin Assembly/disassemblyRapid cell shape changesMuscle contraction Sarcomere Myosin (class II) Linear stepperCytokinesis Division furrow Myosin (class II) Linear stepperStalked ciliate recoil Spasmoneme Spasmin Prestressed springAcrosome extension (Thyone) Acrosomal vesicle Actin AssemblyAcrosome extension (Limulus) Acrosomal bundle Actin Prestressed springdevelopment by the motile behavior of nerve cells, whichsend projections crawling along molecularly defined paths toconnect peripheral body parts to the central nervous system.After spinal cord injuries, these connections are broken, buta medical treatment that encouraged nerve cells to reacquirethe ability to produce motile projections might speed recoveryand reverse paralysis. Defects in cell motility during fetaldevelopment are responsible for many common birth defects,including cleft palate and spina bifida. Other kinds of cellmotility defects are responsible for a variety of conditions,ranging from male infertility to hereditary deafness to thesusceptibility to lung infections seen in people with cysticfibrosis. Cell motility also underlies wound healing and theimmune response.The burgeoning field of nanotechnology offers anotherarea in which detailed knowledge of the mechanisms of cellmotility might prove useful. Cells have spent several billionyears developing highly efficient machinery to generate forcesin the piconewton-to-nanonewton range that operate overdistances of nanometers to micrometers and function well inan aqueous environment. As we grow to better understand themechanics of cell motility, we may be able to adapt the cellmovement machinery for design and engineering purposes.Nanoscale sensors and
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