CELLULAR MECHANOTRANSDUCTION ‘‘Mechanotransduction’’isthetermfortheability,firstdescribedbynineteenth- centuryanatomistJuliusWolff,oflivingtissuestosensemechanicalstressand respondbytissueremodeling.Morerecently,thescopeofmechanotransduction hasbeenexpandedtoincludethesensationofstress,itstranslationintoabio- chemicalsignal,andthesequenceofbiologicalresponsesitproduces.Thisbook looksatmechanotransductioninamorerestrictedsense,focusingonthepro- cessofstresssensingandtransducingamechanicalforceintoacascadeofbio- chemicalsignals.Thisstresshasbecomeincreasinglyrecognizedasoneofthe primaryandessentialfactorscontrollingbiologicalfunctions,ultimatelyaffect- ing the function of the cells, tissues, and organs. A primary goal of this broad book is also to help define the new field of mechanomics, which attempts to describethecompletemechanicalstateofabiologicalsystem. Dr.MohammadR.K.MofradiscurrentlyAssistantProfessorofBioengineer- ing at the University of California, Berkeley, where he is also an affiliated faculty member of graduate programs in applied science and technology and biophysics. Dr. Mofrad received his B.A.Sc. degree from Sharif University of Technology.AfterearningM.A.Sc.andPh.D.degreesfromtheUniversitiesof Waterloo and Toronto, respectively, he spent two years at MIT and Harvard Medical School/Massachusetts General Hospital as a post-doctoral Fellow. Before joining the faculty at Berkeley, Dr. Mofrad was a Principal Research ScientistatMITfornearlytwoyears.AtBerkeley,hehasdevelopedandtaught several courses, including Cell Mechanics and Mechanotransduction and Molecular Cell Biomechanics. He is the founder of the Mechanotransduction KnowledgebaseWebsite,mechanotransduction.org. Dr.RogerD.Kammhaslongbeeninterestedinbiomechanics,beginningwithhis workinvascularandpulmonaryphysiologyandleadingtohismorerecentwork incellandmolecularmechanicsinthecontextofcellularresponsestomechanical stress.Dr.KammhasbeenonthefacultyatMITsincereceivinghisPh.D.in1977 andnowholdsajointappointmentintheBiologicalEngineeringandMechan- ical Engineering Departments. He is currently the Chair of the U.S. National CommitteeonBiomechanicsandtheWorldCouncilonBiomechanics,andheis DirectoroftheGlobalEnterpriseforMicroMechanicsandMolecularMedicine. Kammhasalong-standinginterestinbioengineeringeducation,directsaNational InstituteofHealth–fundedbiomechanicstrainingprogram;co-chairedthecom- mittee to form MIT’s new undergraduate major in biological engineering; and helpedtodevelopMIT’scourseonmolecular,cellular,andtissuebiomechanics. Cellular Mechanotransduction diverse perspectives from molecules to tissues Edited by Mohammad R. K. Mofrad UniversityofCaliforniaBerkeley Roger D. Kamm MassachusettsInstituteofTechnology cambridgeuniversitypress Cambridge,NewYork,Melbourne,Madrid,CapeTown,Singapore, Sa˜oPaulo,Delhi,Dubai,Tokyo CambridgeUniversityPress 32AvenueoftheAmericas,NewYork,NY10013-2473,USA www.cambridge.org Informationonthistitle:www.cambridge.org/9780521895231 (cid:2)CambridgeUniversityPress2010 Thispublicationisincopyright.Subjecttostatutoryexception andtotheprovisionsofrelevantcollectivelicensingagreements, noreproductionofanypartmaytakeplacewithoutthewritten permissionofCambridgeUniversityPress. Firstpublished2010 PrintedintheUnitedStatesofAmerica AcatalogrecordforthisbookisavailablefromtheBritishLibrary. LibraryofCongressCataloginginPublicationData Mofrad,MohammadR.K. Cellularmechanotransduction:diverseperspectivesfrommoleculestotissues/ editedbyMohammadMofrad,RogerKamm. p.cm. Includesbibliographicalreferencesandindex. ISBN978-0-521-89523-1(hardback) 1.Cells–Mechanicalproperties.I.Kamm,RogerD.II.Title. QH645.5.M642009 571.6–dc22 2008049985 ISBN978-0-521-89523-1Hardback CambridgeUniversityPresshasnoresponsibilityforthepersistenceoraccuracyofURLs forexternalorthird-partyInternetWebsitesreferredtointhispublicationanddoesnot guaranteethatanycontentonsuchWebsitesis,orwillremain,accurateorappropriate. Contents Contributors pagevii Preface xi 1. Introduction RogerD.KammandMohammadR.K.Mofrad. . . . . . . . . . . . . . . 1 2. EndothelialMechanotransduction PeterF.DaviesandBrianP.Helmke . . . . . . . . . . . . . . . . . . . 20 3. Role ofthePlasmaMembraneinEndothelialCell Mechanosensation ofShearStress PeterJ.ButlerandShuChien . . . . . . . . . . . . . . . . . . . . . . . 61 4. Mechanotransduction byMembrane-MediatedActivation ofG-ProteinCoupledReceptorsandG-Proteins Yan-LiangZhang,JohnA.Frangos,andMirianasChachisvilis . . . . . . 89 5. CellularMechanotransduction: Interactionswiththe Extracellular Matrix AndrewD.DoyleandKennethM.Yamada . . . . . . . . . . . . . . . . 120 6. Role ofIonChannelsinCellularMechanotransduction –Lessons from theVascular Endothelium AbdulI.BarakatandAndreaGojova . . . . . . . . . . . . . . . . . . . 161 7. TowardaModularAnalysis ofCellMechanosensingand Mechanotransduction: AManual forCellMechanics BenjaminJ.Dubin-ThalerandMichaelP.Sheetz . . . . . . . . . . . . . 181 8. TensegrityasaMechanismforIntegratingMolecularand CellularMechanotransduction Mechanisms DonaldE.Ingber . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196 9. Nuclear MechanicsandMechanotransduction ShinjiDeguchiandMasaakiSato. . . . . . . . . . . . . . . . . . . . . . 220 v vi Contents 10. Microtubule BendingandBreakinginCellular Mechanotransduction AndrewD.Bicek,DominiqueSeetapun,andDavidJ.Odde . . . . . . . 234 11. AMolecularPerspectiveonMechanotransduction in FocalAdhesions SeungE.Lee,RogerD.Kamm,andMohammadR.K.Mofrad. . . . . . 250 12. ProteinConformationalChange:AMolecularBasisof Mechanotransduction GangBao . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269 13. TranslatingMechanical ForceintoDiscrete Biochemical SignalChanges:MultimodularityImposesUniqueProperties toMechanotransductiveProteins VesaP.Hyto¨nen,MichaelL.Smith,andViolaVogel . . . . . . . . . . . 286 14. Mechanotransduction throughLocalAutocrineSignaling NikolaKojicandDanielJ.Tschumperlin . . . . . . . . . . . . . . . . . 339 15. TheInteractionbetweenFluid-WallShearStressandSolid Circumferential StrainAffects EndothelialCellMechanobiology JohnM.Tarbell. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360 16. Micro-andNanoscale ForceTechniquesforMechanotransduction NathanJ.Sniadecki,WesleyR.Legant,andChristopherS.Chen. . . . . 377 17. Mechanical RegulationofStemCells:Implications inTissue Remodeling KyleKurpinski,RandallR.R.Janairo,ShuChien,andSongLi . . . . . 403 18. Mechanotransduction:Role ofNuclearPore Mechanics andNucleocytoplasmic Transport ChristopherB.WolfandMohammadR.K.Mofrad. . . . . . . . . . . . 417 19. SummaryandOutlook MohammadR.K.MofradandRogerD.Kamm. . . . . . . . . . . . . . 438 Index 445 Colorplatesfollowpage180 Contributors GangBao PeterF.Davies DepartmentofBiomedicalEngineering DepartmentofPathologyand GeorgiaInstituteofTechnologyand LaboratoryMedicine EmoryUniversity InstituteforMedicineand Engineering AbdulI.Barakat UniversityofPennsylvania DepartmentofMechanicaland AeronauticalEngineering ShinjiDeguchi UniversityofCalifornia,Davis GraduateSchoolofNaturalScienceand Technology AndrewD.Bicek OkayamaUniversity DepartmentofBiomedicalEngineering UniversityofMinnesota AndrewD.Doyle NationalInstituteofDentaland PeterJ.Butler CraniofacialResearch DepartmentofBioengineering NationalInstitutesofHealth ThePennsylvaniaStateUniversity MirianasChachisvilis BenjaminJ.Dubin-Thaler LaJollaBioengineeringInstitute CellMotionLaboratories,Inc. LaJolla,California JohnA.Frangos ChristopherS.Chen LaJollaBioengineeringInstitute DepartmentofBioengineering LaJolla,California UniversityofPennsylvania ShuChien AndreaGojova DepartmentsofBioengineeringand DepartmentofMechanicaland Medicine AeronauticalEngineering UniversityofCalifornia,SanDiego UniversityofCalifornia,Davis vii viii Contributors BrianP.Helmke MohammadR.K.Mofrad DepartmentofBiomedicalEngineering DepartmentofBioengineering UniversityofVirginia UniversityofCalifornia,Berkeley VesaP.Hyto¨nen DavidJ.Odde LaboratoryofBiologicallyOriented DepartmentofBiomedical Materials,DepartmentofMaterials Engineering ETHZurich UniversityofMinnesota DonaldE.Ingber MasaakiSato DepartmentsofPathologyandSurgery DepartmentofBioengineeringand HarvardMedicalSchoolandChildren’s Robotics Hospital TohokuUniversity RandallR.R.Janairo DepartmentofBioengineering DominiqueSeetapun UniversityofCalifornia,Berkeley DepartmentofBiomedical Engineering RogerD.Kamm UniversityofMinnesota DepartmentsofMechanicalEngineering andBiologicalEngineering MichaelP.Sheetz MassachusettsInstituteofTechnology DepartmentofBiologicalSciences ColumbiaUniversity NikolaKojic Harvard-MITDivisionofHealth MichaelL.Smith ScienceandTechnology LaboratoryofBiologicallyOriented Boston,Massachusetts Materials,DepartmentofMaterials ETHZurich KyleKurpinski DepartmentofBioengineering NathanJ.Sniadecki UniversityofCalifornia,Berkeley DepartmentofBioengineering UniversityofPennsylvania SeungE.Lee DepartmentofBioengineering UniversityofCalifornia,Berkeley JohnM.Tarbell DepartmentofBiomedical WesleyR.Legant Engineering DepartmentofBioengineering TheCityCollegeofNewYork UniversityofPennsylvania DanielJ.Tschumperlin SongLi MolecularandIntegrativePhysiological DepartmentofBioengineering Sciences UniversityofCalifornia,Berkeley HarvardSchoolofPublicHealth