title: A mechanical model of actin stress fiber formation and substrate elasticity sensing in adherent cells.
abstract: Tissue cells sense and respond to the stiffness of the surface on which they adhere. Precisely how cells sense surface stiffness remains an open question, though various biochemical pathways are critical for a proper stiffness response. Here, based on a simple mechanochemical model of biological friction, we propose a model for cell mechanosensation as opposed to previous more biochemically based models. Our model of adhesion complexes predicts that these cell-surface interactions provide a viscous drag that increases with the elastic modulus of the surface. The force-velocity relation of myosin II implies that myosin generates greater force when the adhesion complexes slide slowly. Then, using a simple cytoskeleton model, we show that an external force applied to the cytoskeleton causes actin filaments to aggregate and orient parallel to the direction of force application. The greater the external force, the faster this aggregation occurs. As the steady-state probability of forming these bundles reflects a balance between the time scale of bundle formation and destruction (because of actin turnover), more bundles are formed when the cytoskeleton time-scale is small (i.e., on stiff surfaces), in agreement with experiment. As these large bundles of actin, called stress fibers, appear preferentially on stiff surfaces, our mechanical model provides a mechanism for stress fiber formation and stiffness sensing in cells adhered to a compliant surface.
authors.affiliation: Mechanical Engineering and Johns Hopkins Physical Science Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Walcott
authors.forename: Sean X
authors.initials: SX
authors.lastname: Sun
mesh_terms: D000199:Actins / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D001696:Biomechanical Phenomena; D002448:Cell Adhesion / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism / Q000502:physiology*; D004548:Elasticity / Q000502:physiology; D017276:Friction / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D000199:Actins; D009218:Myosins
references.citation: Science. 2005 Nov 18;310(5751):1139-43
references.pmid: 16293750
references.citation: Biochemistry. 2004 Apr 13;43(14):4219-26
references.pmid: 15065866
references.citation: J Mol Biol. 2001 Jul 6;310(2):351-66
references.pmid: 11428894
references.citation: Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H284-91
references.pmid: 17351073
references.citation: Cell Motil Cytoskeleton. 1993;24(4):215-23
references.pmid: 8477454
references.citation: J Cell Sci. 2008 Jan 1;121(Pt 1):11-8
references.pmid: 18096687
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2009 Oct;80(4 Pt 2):046124
references.pmid: 19905407
references.citation: Cell Motil Cytoskeleton. 2005 Jan;60(1):24-34
references.pmid: 15573414
references.citation: Biophys J. 2005 Nov;89(5):3589-602
references.pmid: 16085776
references.citation: Biochem Biophys Res Commun. 2004 Jan 16;313(3):758-64
references.pmid: 14697256
references.citation: Nat Cell Biol. 2008 Sep;10(9):1039-50
references.pmid: 19160484
references.citation: Eur Phys J E Soft Matter. 2005 Jan;16(1):5-16
references.pmid: 15688136
references.citation: J Biol Chem. 2009 Jul 3;284(27):18244-51
references.pmid: 19419961
references.citation: Biophys J. 2005 Aug;89(2):782-95
references.pmid: 15879474
references.citation: Biophys J. 2006 Jan 1;90(1):65-76
references.pmid: 16214866
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12520-5
references.pmid: 15314229
references.citation: Biophys J. 2003 Feb;84(2 Pt 1):1328-36
references.pmid: 12547813
references.citation: Science. 2004 May 28;304(5675):1301-5
references.pmid: 15166374
references.citation: J Cell Sci. 2001 Oct;114(Pt 20):3583-90
references.pmid: 11707510
references.citation: Biophys J. 2008 Feb 15;94(4):1470-82
references.pmid: 17933882
references.citation: Phys Chem Chem Phys. 2009 Jun 28;11(24):4871-81
references.pmid: 19506762
references.citation: Phys Rev Lett. 2004 Feb 20;92(7):078101
references.pmid: 14995891
references.citation: Nat Rev Mol Cell Biol. 2009 Jan;10(1):21-33
references.pmid: 19197329
references.citation: Cell. 2006 Aug 25;126(4):677-89
references.pmid: 16923388
references.citation: Biophys J. 2005 Nov;89(5):L34-6
references.pmid: 16169988
references.citation: Nat Cell Biol. 2000 Apr;2(4):191-6
references.pmid: 10783236
references.citation: Science. 2004 Sep 17;305(5691):1782-6
references.pmid: 15375270
references.citation: J Biol Chem. 2006 Nov 24;281(47):35873-83
references.pmid: 17020881
references.citation: Science. 2008 Dec 12;322(5908):1687-91
references.pmid: 19074349