Modeling and simulation of cell adhesion and detachment

MODELING AND SIMULATION OF CELL ADHESION AND DETACHMENT SUN LU NATIONAL UNIVERSITY OF SINGAPORE 2011 MODELING AND SIMULATION OF CELL ADHESION AND DETACHMENT SUN LU (B. Eng., FDU China) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF MATERIALS SCIENCE AND ENGINEERING NATIONAL UNIVERSITY OF SINGAPORE 2011 Acknowledgement I would like to express my most sincere gratitude to my supervisor Dr. Zhang Yongwei for his continuous encouragement, guidance, and great inspirations throughout the years of my PhD study. Dr. Zhang has been immensely supportive as I faced all the hurdles in my research work. I am deeply grateful to my co-supervisor, Dr. Cheng Qianghua for his generous helps through the several projects over the past years. Without his guidances, the completion of my thesis would not have been possible. I also want to thank my colleague Wu Zhaoxuan for his great efforts in maintaining our PC clusters. Special thanks to my colleague and friend Zhang Xiaoxin for her selfless help. I am grateful for the friendship with Koh Tiong-Soon, Hu Guangxia, Yi Jiabao, Han Zheng, Yu Jun, and Wang Yu. The wonderful time we have spent together in NUS will stay in my heart forever. My heartfelt gratitude goes to my beloved mother Xu Yili, who has taken care of me with great love in all the past years. I wish to deeply thank my father Sun Buyue, who has always been my role model and my spiritual support. Last but not least, I thank Hugo Willy, for all the love. i Contents Summary iv List of Figures vi Introduction . 1.1 Motivations 1.2 Objectives 1.3 Thesis Outline and Overview Background Information 2.1 Structures and Functions of Cell . 2.2 Basics of Cell Adhesion 12 2.2.1 Nonspecific Interactions 13 2.2.2 Specific Interactions . 15 2.2.3 Receptor Mobility . 16 2.3 An Introduction to Biomimetic Systems . 17 2.4 Techniques in Quantifying Cell Adhesions . 18 2.4.1 Lifetime of Loaded Single Bond 19 2.4.2 Relevant Length and Force Scales 20 2.4.3 Ultrasensitive Probes 21 2.4.4 Ensemble Effect of Multiple Bonds 25 2.5 Modeling and Simulation Methods . 26 A Computational Model for Cell Adhesion . 29 3.1 Representative Models of Cell Adhesion 29 3.1.1 Equilibrium Thermodynamics Framework . 30 3.1.2 Cohesive Zone Models . 32 3.1.3 Kinetic Models Involving Nucleation and Growth Process 33 3.2 Issues Remaining Disputed 34 3.3 Model Formulation . 35 3.3.1 Non-specific Interaction between Receptors and Substrate . 36 3.3.2 Specific Interaction between Receptors and Ligands . 38 3.3.3 Receptor Diffusion on Cell Membrane . 39 3.3.4 Model Formulation for Vesicle Structure and Substrate 40 3.4 Simulation Model and Numerical Procedure 41 3.5 Simulation Results 43 3.5.1 Simulation Results for a Typical Case 43 3.5.2 Parametric Studies of System Parameters . 47 3.6 Discussion and Conclusions . 55 A Computational Model for Biomembrane Force Probe (BFP) . 57 4.1 An Introduction of Previous BFP Studies . 58 ii 4.2 Computational Model and Simulation Procedure . 61 4.2.1 Model Formulation 61 4.2.2 Simulation Procedure . 62 4.3 Simulation Results 63 4.3.1 Force-Deflection Relations for Different Aspiration Pressures 64 4.3.2 Force-Deflection Relations for Different Micropipette Radii . 68 4.4 Analytical Study of Nonlinear Characteristic Regime 70 4.4.1 Model Formulation and Analysis 70 4.4.2 Results and Analysis . 73 4.5 Discussion and Conclusions . 77 Dynamics of Catch-Slip Bond Clusters under Constant Force 81 5.1 Catch Bond Assumptions and Discoveries . 81 5.2 Catch Bond Models 82 5.2.1 Conceptual Models for Catch Bonds 82 5.2.2 Quantitative Models for Catch Bonds 84 5.3 Multiple-Bond Systems 88 5.4 Simulation Results 90 5.4.1 System Parameters . 90 5.4.2 Lifetime of Single Bond 90 5.4.3 Lifetime of Parallel Multiple Bonds with Uniformly Distributed Force . 92 5.4.4 Lifetime of Multiple Bonds with Non-uniformly Distributed Force 98 5.4.5 The Micropipette-Manipulated Detachment of a Cell from a Substrate Surface 102 5.5 Discussions and Conclusions . 105 Conclusions and Future Research . 108 6.1 Conclusions . 108 6.2 Future Research 110 Bibliography . 112 iii Summary The adhesion between two cells and between the cell and its extracellular matrix play an integral role in a large variety of biological processes. In the recent decade, the development of technologies for probing and manipulating single cells at minuscule forces has allowed studies on cellular interactions to advance to the individual molecular level. This thesis aims to provide in-depth understanding of the mechanics and kinetics of cell adhesion and detachment through biophysical modeling and computer simulation on intercellular interactions. We present our results in three parts. First, we design a computational model of cell adhesion to a substrate surface.which incorporate three major factors: the non-specific forces, specific bindings, and the diffusion of adhesive binders. Through a series of system parametric studies, our model identified three possible limiting regimes for cell adhesions: 1) the binder reaction limited regime, 2) non-specific, force-driven, binder recruitment limited regime, and 3) the concentration gradient-driven diffusion limited regime. Among them the slowest process will be the major limiting factor to the adhesion. In the second part, we investigate the accuracy and sensitivity of Biomembrane Force Probe (BFP), a popular technique for the minuscule force measurement. Through finite element simulations and semi-analytical analysis, we discovered a characteristic non-linear regime. This finding is an important iv amendment to the existing BFP modeling, which only considers a linear relation between the BFP stiffness and its micropipette aspiration pressure. We further identified the critical conditions for the transition between the linear and nonlinear regimes. This could be an important reference for experimentalists to avoid using formulas intended for the linear regime on the non-linear one. In the final part, we examine the effect of catch-slip mechanism on multiple-bond decohesions. To this end, we performed computational analysis on three scenarios, 1) the dissociation of single bond under constant forces, 2) the dissociation of bond clusters under uniform and linearly increasing force distributions, and 3) micropipette-manipulated cell dissociation from a substrate surface. Our computation reveals that, for a multiple-bond cluster, the catch bond behavior could only be observed under relatively uniform loading condition and only at certain stage of decohesion. Our model thus offers an explanation on the difficulties of observing the catch bond behavior under real biological conditions. v List of Figures Figure 2.1 A simplified illustration of eukaryotic cell structure . Figure 2.2 A simplified illustration of cell membrane Figure 2.3 Sketch of ultrasensitive force probes. 22 Figure 3.1 Illustration of one-dimensional tape peeling model for cell adhesion. . 32 Figure 3.2 Schematic of vesicle adhesion mediated by the diffusion of the receptors and the binding of the receptor-ligand pairs 35 Figure 3.3 Variation of receptor density caused by diffusion of the receptors on the cell surface. . 37 Figure 3.4 The curve of binding area vs. spreading time for the typical case. 44 Figure 3.5 The curves of total normalized specific forces (solid line) and the total number of receptor-ligand bonds (dashed line) vs. spreading time for the typical case. 46 Figure 3.6 Distribution of the normalized receptor density (ρr/ρr0) along the normalized arc length (s/a0) at different stages of spreading with ac /a0 = 0.97, 1.02, and 1.03 . 46 Figure 3.7 The curves of binding area vs. spreading time at different non-specific force coefficient H. . 49 Figure 3.8 The curves of binding area vs. spreading time at different non-specific force cut-off distance 1c 49 Figure 3.9 Distribution of the normalized receptor density (2r/2r0) along the normalized arc length (s/a0) at the final stage of spreading with different H. . 50 Figure 3.10 The curves of binding area vs. spreading time at different forward reaction rate coefficient k 0f 51 Figure 3.11 Distribution of the normalized receptor density (ρr/ρr0) along the vi normalized arc length (s/a0) at the final stage of spreading with different k 0f 52 Figure 3.12 The curves of binding area vs. spreading time at different specific characteristic length δb . 53 Figure 3.13 Distribution of the normalized receptor density (ρr/ρr0) along the normalized arc length (s/a0) at the final stage of spreading with different δb . 53 Figure 3.14 The curves of binding area vs. spreading time at different reverse reaction coefficient kr0 . 54 Figure 4.1 Schematic of a BFP setting . 59 Figure 4.2 Simulated force-deflection relations at different levels of the aspiration pressure ∆P . 65 Figure 4.3 Membrane tension along the cell arc length at different phases of simulations. Membrane tension change at (a) ∆P = 1000 Pa and (b) ∆P = 37.5 Pa . 66 Figure 4.4 Comparison of BFP spring constants between the present simulation results and Simson’s results. . 67 Figure 4.5 FEM results of force-deflection relations at different micropipette radii Rp 69 Figure 4.6 FEM results of stiffness-aspiration pressure relations at different micropipette radii Rp . 69 Figure 4.7 Simulated membrane configuration in the nonlinear characteristic regime. 71 Figure 4.8 Semi-analytical results of force-deflection relations at different levels of the aspiration pressure ∆P 74 Figure 4.9 Comparison of the calculated stiffness constants between FEM simulations (square dots) and the semi-analytical model (round dots) . 75 Figure 4.10 The relationship between critical aspiration pressure and micropipette radius 76 vii Figure 4.11 The relationship between critical extension force and aspiration pressure for different micropipette radius. 77 Figure 5.1 A simple illustration of two conceptual catch bond models 84 Figure 5.2 Single bond lifetime as functions of loading force for both slip and catch-slip bond models . 91 Figure 5.3 Schematic illustration of a bond cluster under constant force F. F is equally shared by all closed bonds 92 Figure 5.4 Bond number changes as functions of time t for different loading forces; (a) slip bond model and (b) catch-slip bond model 94 Figure 5.5 Rupture time as functions of loading force at different decohesion stages: (a) slip bond model; (b) catch-slip bond model 96 Figure 5.6 Parallel multiple bond lifetime as functions of loading force for slip and catch-slip models 97 Figure 5.7 Schematic illustration of a catch-slip bond cluster under constant loading force F. An inclined angle is kept between the two plates, so the force is nonuniformly distributed on each row of bonds. . 98 Figure 5.8 Bond number as functions of time t for different loadings (Left). And rupture time as functions of loading forces at different stages of decohesion (Right). Three cases with different values of are demonstrated: (a) tg3 = 0.1; (b) tg3 = 0.2; (c) tg3 = 0.3. 100 Figure 5.9 Rupture time as functions of loading force at different decohesion stages . 104 viii Lond. B. 234, 55 (1988). The Reaction-Limited Kinetics of Membrane-to-Surface Adhesion and Detachment. [26] T. Erdmann, S. Pierrat, P. Nassoy, and U.S. Schwarz, Europhys. Lett. 81, 48001 (2008). Dynamic force spectroscopy on multiple bonds: Experiments and model. [27] H.J. Gao, W. Shi and L.B. Freund, Proc. Natl. Acad. Sci. USA. 102, 9469 (2005). Mechanics of receptor-mediated endocytosis. [28] P. Liu, Y.W. Zhang, Q.H. Cheng, C. Lu, J. Mech. Phys. Solids 55, 1166 (2007). Simulations of the spreading of a vesicle on a substrate surface mediated by receptor-ligand binding. [29] G. Binning, C.F. Quate, C.H. Gerber, Phys. Rev. Lett. 56, 930 (1986). Atomic force microscope. [30] S.C. Kuo, M.P. Sheetz, Science. 260, 232 (1993). Force of single kinesin molecules measured with optical tweezers. [31] E. Evans, K. Ritchie, R. Merkel, Biophys. J. 68, 2580 (1995). Sensitive force technique to probe molecular adhesion and structural linkages at biological interfaces. [32] D.A. Simson, F, Ziemann, M. Strigl, R. Merkel, Biophys. J. 74, 2080 (1998). Micropipet-based pico force transducer: in depth analysis and experimental verification. [33] V. Heinrich, C. Ounkomol, Biophys. J. 93, 363 (2007). Force versus axial deflection of pipette-aspirated closed membranes. 115 [34] L.B. Freund, Math. Mech. Solids. 14, 148 (2009). The Stiffness of a Biomembrane Force Probe Vesicle. [35] E. Evans, V. Heinrich, A. Leung, K. Kinoshita, Biophys. J. 88, 2288 (2005). Nano- to microscale dynamics of P-selectin detachment from leukocyte interfaces. I. Membrane separation from the cytoskeleton. [36] V. Heinrich, A. Leung, E. Evans, Biophys. J. 88, 2299 (2005). Nano- to microscale dynamics of P-selectin detachment from leukocyte interfaces. II. Tether flow terminated by P-selectin dissociation from PSGL-1. [37] M.R. King, V. Heinrich, E. Evans, D.A. Hammer, Biophys. J. 88, 1676 (2005). Nano-to-microscale dynamics of P-selectin detachment from leukocyte interfaces. III. Numerical simulation of tethering under flow. [38] V. Heinrich, A. Leung, E. Evans, J. Chem. Inf. Model. 45, 1482 (2005). Nano-to-microscale mechanical switches and fuses mediate adhesive contacts between leukocytes and the endothelium. [39] A. Jegou, F. Pincet, E. Perez, J.P. Wolf, A. Ziyyat, C. Gourier, Langmuir 24, 1451 (2008). Mapping mouse gametes interaction forces reveals several oocyte membrane regions with different mechanical and adhesive properties. [40] V. Heinrich, K. Ritchie, N. Mohandas, E. Evans, Biophys. J. 81, 1452 (2001). Elastic thickness compressibility of the red cell membrane. [41] S. Pierrat, F. Brochart-Wyart, P. Nassoy, Biophys. J. 87, 2855 (2004). Enforced detachment of red blood cells adhering to surfaces: statics and 116 dynamics. [42] E.B. Finger, K.D. Purl, R. Alon, M.B. Lawrence, U.H. Andrian, T.A. Springer, Nature 379, 266 (1996). Adhesion through L-selectin requires a threshold hydrodynamic shear. [43] T.A. Doggett, G. Girdhar, A. Lawshe, D.W. Schmidtke, I.J. Laurenzi, S.L. Diamond, T.G. Diacovo, Biophys. J. 83, 194 (2002). Selectin-Like Kinetics and Biomechanics Promote Rapid Platelet Adhesion in Flow: The GPIb1-vWF Tether Bond. [44] B.T. Marshall, M. Long, J.W. Piper, T. Yago, R.P. McEver, C. Zhu, Nature 423, 190 (2003). Direct observation of catch bonds involving cell-adhesion molecules. [45] V. Barsegov, D. Thirumalai, Proc. Natl. Acad. Sci. USA. 102, 1835 (2005). Dynamics of unbinding of cell adhesion molecules: Transition from catch to slip bonds. [46] E. Evans, A. Leung, V. Heinrich, C. Zhu, Proc. Natl. Acad. Sci. USA. 101, 11281 (2004). Mechanical switching and coupling between two dissociation pathways in a P-selectin adhesion bond. [47] Y.V. Pereverzev, O.V. Prezhdo, M. Forero, E.V. Sokurenko, W.E. Thomas, Biophys. J. 89, 1446 (2005). The two-pathway model for the catch-slip transition in biological adhesion. [48] W.T. Thomas, M. Forero, O. Yakovenko, L. Nilsson, P. Vicini, E. Sokurenko, V. Vogel, Biophys. J. 90, 753 (2006). Catch-bond model 117 derived from allostery explains force-activated bacterial adhesion. [49] B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, Molecular Biology of the Cell, Fourth Edition, (Garland Science, New York, 2002). [50] K.H. Nierhaus, D.N. Wilson, Protein Synthesis and Ribosome Structure, (Wiley-VCH, 2004). [51] T.R. Cech, Science 289, 878 (2000). Structural biology. The ribosome is a ribozyme. [52] K. Henze, W. Martin, Nature 426, 127 (2003). Evolutionary biology: essence of mitochondria. [53] J.P. Luzio, P.R. Pryor, N.A. Bright, Nat. Rev. Mol. Cell Biol. 8, 622 (2007). Lysosomes: fusion and function. [54] G.J. Doherty, H.T. McMahon, Ann. Rev. Biophys. 3, 65 (2008). Mediation, Modulation, and Consequences of Membrane-Cytoskeleton Interactions. [55] E. Zamir, B. Gerger, J. Cell Sci. 114, 3583 (2001). Molecular complexity and dynamics of cell-matrix adhesions. [56] N.Q. Balaban, U.S. Schwarz, D. Riveline, Nat. Cell Biol. 3, 466 (2001). Force and focal adhesion assembly: a close relationship studied using elastic micro-patterned substrate. [57] G.C. Maitland, M. Rigby, E.B. Smith, W.A. Wakeman, Intermolecular Forces: Their Origin and Determination, (Clarendon Press, Oxford, 118 1981). [58] V.A. Parsegian, D. Gingell, J. Cell Sci. 41, 151 (1980). Red blood cell adhesion. III. Analysis of forces. [59] W. Helfrich, R.M. Servuss, Nuovo Cimento 3D, 137 (1984). Undulations, steric interaction and cohesion of fluid membranes. [60] S. Felder, E.L. Elson, J. Cell Biol. 111, 2513 (1990). Mechanics of fibroblast locomotion: quantitative analysis of forces and motions at the leading lamellas of fibroblasts. [61] M.S. Kolodney, R.B. Wilsomerski, J. Cell Biol. 117, 73 (1992). Isometric contraction by fibroblasts and endothelial cells in tissue culture: a quantitative study. [62] D.A. Lauffenburger, J. Linderman, Receptors: Models for Binding, Trafficking and Signalling (Oxford University Press, Oxford, 1993). [63] F. Sánchez-Madrid, A.L. Corbí, Semin. Cell. Biol. 3,199 (1992). Leukocyte integrins: Structure, function and regulation of their activity. [64] T.A. Springer, Annu. Rev. Cell Biol. 6, 359 (1990). The sensation and regulation of interactions with the extracellular environment: The cell biology of lymphocyte adhesion receptors. [65] A. Salas, M. Shimaoka, U. Phan, M. Kim, T.A. Springer, J. Biol. Chem. 281, 10876 (2006). Transition from rolling to firm adhesion can be mimicked by extension of integrin aLb2 in an intermediate-affinity state. [66] R.J. Cherry, P.R. Smith, I.E. Morrison, N. Fernandez, FEBS Lett. 430, 119 88 (1998). Mobility of cell surface receptors: a re-evaluation. [67] M. Lippert, T.H. Bruckel, T.H. Kohler, J.R. Schneider, Europhys. Lett. 27, 537 (1994). High-Resolution Bulk Magnetic Scattering of High-Energy Synchrotron Radiation. [68] D. Cuvelier, P. Nassoy, Phys. Rev. Lett. 93, 228101 (2004). Hidden dynamics of vesicle adhesion induced by specific stickers. [69] L.A. Bagatolli, Biochim. Biophys. Acta 1758, 1541 (2006). To see or not to see: lateral organization of biological membranes and fluorescence microscopy. [70] F.M. Menger, J.S. Keiper, Curr. Opin. Chem. Biol. 2, 726 (1998). Chemistry and physics of giant vesicles as biomembrane models. [71] S.L. Veatch, S.L. Keller, Biochim. Biophys. Acta 1746, 172 (2005). Seeing spots: complex phase behavior in simple membranes. [72] J. Bernardino, J. Perez-Gil, A.C. Simonsen, L.A. Bagatolli, J. Biol. Chem. 279, 40715 (2004). Cholesterol rules: direct observation of the coexistence of two fluid phases in native pulmonary surfactant membranes at physiological temperatures. [73] K.L. Johnson, K. Kendall, A.D. Roberts, Proc. R. Soc. London, Ser. A 324, 301 (1971). Surface Energy and the Contact of Elastic Solids. [74] G. Lee, S.K. Kang, D. Kwon, Mater. Sci. Eng., A 496, 494 (2008). Characterization of elastic modulus and work of adhesion in elastomeric polymers using microinstrumented indentation technique. 120 [75] M. Schlierf, H.B. Li, and J.M. Fernandez. Proc. Natl. Acad. Sci. 101, 7299 (2004). The unfolding kinetics of ubiquitin captured with single-molecule force-clamp techniques. [76] E.L. Florin, V.T. Moy, H.E. Gaub, Science 264, 415 (1994). Adhesion forces between individual ligand-receptor pairs. [77] M. Favre, S.K. Sekatskiia, G. Dietler, Ultramicroscopy 108, 1135 (2008). Single-molecule avidin–biotin association reaction studied by force-clamp spectroscopy. [78] E. Evans, Annu. Rev. Biophys. Biomol. Struct. 30, 105 (2001). Probing the relation between force-lifetime-and chemistry in single molecular bonds. [79] L. Reimer, Scanning Electron Microscopy: Physics of Image Formation and Microanalysis (Springer, Berlin, 1998). [80] D.E. Leckband, F.J. Schmitt, W. Knoll, J.N. Israelachvili, Biochemistry 33, 4611 (1994). Direct force measurements of specific and nonspecific protein interactions. [81] D.E. Leckband, J.N. Israelachvili, F.J. Schmitt, W. Knoll, Science 255, 1419 (1992). Long-Range Attraction and Molecular-Rearrangements in Receptor-Ligand Interactions. [82] A. Ashkin, Biophys. J. 61, 569 (1992). Forces of a single-beam gradient laser trap on a dielectric sphere in the ray optics regime. [83] A. Ashkin, K. Schutze, J.M. Dziedzic, U. Euteneuer, M. Schliwa, Nature, 121 348 (1990). Force generation of organelle transport measured in vivo by an infrared laser trap. [84] R.M. Jeffery, R.C. Yann, B.S. Steven, B. Carlos, Annu. Rev. Biochem. 77, 205 (2008). Recent advances in optical tweezers. [85] R. Vijayendran, D. Hammer, D. Leckband, J. Chem. Phys. 108, 7783 (1998). Simulations of the adhesion between molecularly bonded surfaces in direct force measurements. [86] A. Saterbak, D.A. Lauffenburger, Biotechnol. Prog. 12, 682 (1996). Adhesion mediated by bonds in series. [87] M.S.Z. Kellermayer, S.B. Smith, H.L. Granzier, C. Bustamante, Science 276, 1112 (1997). Folding-unfolding transitions in single titin molecules characterized with laser tweezers. [88] D.C. Rapaport, The Art of Molecular Dynamics Simulation, 2nd Edition (Cambridge University Press, Cambridge, 2004). [89] H. Grandin Jr., Fundamentals of the Finite Element Method (Macmillan, New York, 1986). [90] D.J. Acheson, Elementary Fluid Dynamics (Clarendon Press, Oxford, 1990). [91] D.W. Tank, E.S. Wu, W.W. Webb, J. Cell Biol. 92, 207 (1982). Enhanced molecular diffusibility in muscle membrane blebs: Release of lateral constraints. [92] C.J. Van Oss, J. Disp. Sci. Technol. 12, 201 (1991). Interaction forces 122 between biological and other polar entities in water: How many different primary forces are there? [93] G. Benjamin, B. Alexander, Cell 110, 139 (2002). Exploring the neighborhood: Adhesion coupled cell mechanosensors. [94] C.A. Reinhart-King, M. Dembo, D.A. Hammer, Biophys. J. 89, 676 (2005). The dynamics and mechanics of endothelial cell spreading. [95] C. Damien, N. Pierre, Phys. Rev. Lett. 93, 228101(2004). Hidden dynamics of vesicle adhesion induced by specific stickers. [96] V. Tvergaard, J.W. Hutchsinson, J. Mech. Phys. Solids 41, 1119 (1993). The influence of plasticity on mixed-mode interface toughness. [97] P. Liu, L. Cheng, Y.W. Zhang, Acta Mater. 49, 817-825 (2001). Measuring interface parameters and toughness-a computational study. [98] ABAQUS User’s Manual, Version 6.7 (ABAQUS Inc., Pawtucket, RI, USA, 2007). [99] M. Dao, C.T. Lim, S. Suresh, J. Mech. Phys. Solids. 51, 2259 (2003). Mechanics of the human red blood cell deformed by optical tweezers. [100] C.T. Lim, E.H. Zhou, A. Li, S.R.K. Vedula, H.X. Fu, Mater. Sci. Eng. C 26, 1278 (2006). Experimental techniques for single cell and single molecule biomechanics. [101] J.J. Valle-Delgado, J.A. Molina-Bolivar, F. Galisteo-Gonzalez, M.J. Galvez-Ruiz, A. Feiler, M.W. Rutland, Langmuir 22, 5108 (2006). Adhesion forces between protein layers studied by means of atomic 123 force microscopy. [102] L.B. Freund, Y. Lin, J. Mech. Phys. Solids. 52, 2455 (2004). The role of binder mobility in spontaneous adhesive contact and implications for cell adhesion. [103] D.A. Hammer and D.A. Lauffenburger, Biophys. J. 52: 475 (1987). A Dynamical Model for Receptor-mediated Cell Adhesion to Surfaces. [104] Y.S. Chu, S. Dufour, J.P. Thiery, E. Perez, F. Pincet, Phys. Rev. Lett. 94, 028102 (2005). Probing of depletion induced cell adhesion by micromanipulation and influence of the cytoskeleton. [105] A. Ishijima, T. Doi, K. Sakurada, T. Yanagida, Nature 352, 201 (1991). Sub-piconewton force fluctuations of actomyosin in vitro. [106] E.A. Evans, Biophys. J. 13, 941 (1973). New membrane concept applied to the analysis of fluid shear- and micropipette-deformed red blood cells. [107] R.M. Hochmuth, N. Mohandas, P.L. Blackshear, Biophys. J. 13, 747 (1973). Measurement of the elastic modulus for red cell membrane using a fluid mechanical technique. [108] E.A. Evans, R. Waugh, L. Melnik, Biophys. J. 16, 585 (1976). Elastic area compressibility modulus of red cell membrane. [109] E.A. Evans, R. Waugh, Biophys. J. 20, 307 (1977). Osmotic correction to elastic area compressibility measurements on red cell membrane. [110] E.A. Evans, R. Skalak, Mechanics and Thermodynamics of Biomembranes (CRC Press: Boca Raton, 1980). 124 [111] E. Evans, W. Rawicz, Phys. Rev. Lett. 64, 2094 (1990). Entropy-driven tension and bending elasticity in condensed-fluid membranes. [112] A. Zilker, M. Ziegler, E. Sackmann, Phys. Rev. A. 46, 7998 (1992). Spectral analysis of erythrocyte flickering in the 0.3- 43m-1 regime by microinterferometry combined with fast image processing. [113] P. Ratanabanangkoon, M. Gropper, R. Merkel, E. Sackmann, A.P. Gast, Langmuir 19, 1054 (2003). Mechanics of streptavidin-coated giant Lipid bilayer vesicles: A micropipet study. [114] A.W. Jay, P.B. Canham, Biophys. J. 17, 169 (1977). Viscoelastic properties of the human red blood cell membrane. II. Area and volume of individual red cells entering a micropipette. [115] K.G. Engstrom, H.J. Meiselman, Cytometry 23, 22 (1996). Effects of pressure on red blood cell geometry during micropipette aspiration. [116] V. Heinrich, W. Rawicz, Langmuir 21, 1962 (2005). Automated, high-resolution micropipet aspiration reveals new insight into the physical properties of fluid membranes. [117] C. Ounkomol, H. Xie, P.A. Dayton, V. Heinrich, Biophys. J. 96, 1218 (2009). Versatile horizontal force probe for mechanical tests on pipette-held cells, particles, and membrane capsules. [118] J. Derganc, B. Bozic, S. Svetina, B. Zeks, Biophys. J. 79, 153 (2000). Stability analysis of micropipette aspiration of neutrophils. [119] Y. Lin, L.B. Freund, Int. J. Solids. Struct. 44, 1927 (2007). Forced 125 detachment of a vesicle in adhesive contact with a substrate. [120] D.E. Discher, N. Mohandas, Biophys. J. 71, 1680 (1996). Kinematics of red cell aspiration by fluorescence-imaged microdeformation. [121] C.B. Moler, Numerical Computing with Matlab (Society for Industrial and Applied Mathematics, Philadelphia, 2004). [122] D.V. Zhelev, D. Needham, R.M. Hochmuth, Biophys. J. 67, 696 (1994). Role of the membrane cortex in neutrophil deformation in small pipets. [123] E.A. Evans, Biophys. J. 30, 265 (1980). Minimum energy analysis of membrane deformation applied to pipet aspiration and surface adhesion of red blood cells. [124] H.V. Ly, D.E. Block, M.L. Longo, Langmuir 18, 8988 (2002). Interfacial tension effect of ethanol on lipid bilayer rigidity, stability, and area expansion: A micropipette aspiration approach. [125] S.I. Simon, T. Nyunt, K. Florine-Casteel, K. Ritchie, H.P. Ting-Beall, E. Evans, D. Needham, Ann. Biomed. Eng. 35, 595 (2007). Dynamics of neutrophil membrane compliance and microstructure probed with a micropipet-based piconewton force transducer. [126] E. Evans, A. Yeung, Biophys. J. 56, 151 (1989). Apparent viscosity and cortical tension of blood granulocytes determined by micropipet aspiration. [127] R.M. Hochmuth, J. Biomech. 33, 15 (2000). Micropipette aspiration of living cells. 126 [128] E. Evans, Annu. Rev. Biophys. Biomol. Struct. 30, 105 (2001). Probing the relation between force-life-time-and chemistry in single molecular bonds. [129] K.K. Sarangapani, T. Yago, A.G. Klopocki, M.B. Lawrence, C.B. Fieger, S.D. Rosen, R.P. McEver, C. Zhu, J. Biol. Chem. 279, 2291 (2004). Low force decelerates L-selectin dissociation from P-selectin glycoprotein ligand-1 and endoglycan. [130] V. Tchesnokova,P. Aprikian, O. Yakovenko, C. Larock, B. Kidd, V. Vogel, W. Thomas, E. Sokurenko, J. Biol. Chem. 283, 7823 (2008) Integrin-like allosteric properties of the catch bond-forming FimH adhesin of Escherichia coli. [131] Guo, B., 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, 9844– 9849. (doi: 10.1073/pnas.0601255103) [132] Kong, F., García, A.J., Mould, A.P., Humphries, M.J., Zhu, C., 2009 Demonstration of catch bonds between an integrin and its ligand. J. Cell Biol. 185:1275 [133] D. Bartolo, I. Derenyi, A. Ajdari, Phys. Rev. E 65, 051910 (2002). Dynamic response of adhesion complexes: beyond the single-path picture. [134] R.R. Isberg, P. Barner, Cell 101, (2002). Dancing with the host; flow-dependent bacterial adhesion. 127 [135] O.V. Prezhdo, and Y.V. Perverzev, Acc. Chem. Res. 42, 693 (2009) Theoretical aspects of the biological catch bond. [136] S. Barbaux, O. Poirier, F. Pincet, P. Hermand, L. Tiret, P. Deterre, J. Leukoc. Biol. 87, 4727 (2010). The adhesion mediated by the P-selectin P–selectin glycoprotein ligand-1 (PSGL-1) couple is stronger for shorter PSGL-1 variants. [137] W.E. Thomas, E. Trintchina, M. Forero, V. Vogel, E.V. Sokurenko, Cell 109, 913 (2002). Bacterial adhesion to target cells enhanced by shear force. [138] U. Seifert, Phys. Rev. Lett. 84, 2750 (2000). Rupture of multiple parallel molecular bonds under dynamic loading. [139] K. Prechtel, A.R. Rausch, V. Marchi-Artzner, M. Kantlehner, H. Kessler, R. Merkel, Phys. Rev. Lett. 89, 028101 (2002). Dynamic force spectroscopy to probe adhesion strength of living cells. [140] C.C. Tang, Y.P. Chu, H.Y. Chen, Phys. Rev. E 76, 061905 (2007). Lifetime of ligand-receptor clusters under external force. [141] A. Boulbitch, Eur. Biophys. J. 31, 637 (2003). Enforced unbinding of biomembranes whose mutual adhesion is mediated by a specific interaction. [142] W. Thomas, Annu. Rev. Biomed. Eng. 10, 39 (2008). Catch bonds in adhesion. [143] T. Erdmann and U.S. Schwarz, Phys. Rev. Lett. 92, 108102 (2004). 128 Stability of adhesion clusters under constant force. [144] T. Erdmann and U.S. Schwarz, J. Chem. Phys. 121, 8997 (2004). Stochastic dynamics of adhesion clusters under shared constant force and with rebinding. [145] E. Evans, K. Ritchie, Biophys J. 72, 1541(1997). Dynamic strength of molecular adhesion bonds. [146] Erdmann, T. & Schwarz, U.S. 2007 Impact of receptor-ligand distance on adhesion cluster stability. Eur. Phys. J. E 22, 123-137. (doi: 10.1140/epje/e2007-00019-8) [147] Qian, J., Wang, J. & Gao, H. 2008 Lifetime and strength of adhesive molecular bond clusters between elastic media. Langmuir 24, 1262-1270. (doi: 10.1021/la702401b) [148] Qian, J., Wang, J., Lin, Y. & Gao, H. 2009 Lifetime and strength of periodic bond clusters between elastic media under inclined loading. Biophys. J. 97, 2438-2445. (doi: 10.1016/j.bpj.2009.08.027) [149] Qian, J. & Gao, H. 2010 Soft matrices suppress cooperative behaviors among receptor-ligand bonds in cell adhesion. PLoS ONE 5, e12342 [150] V. Barsegov, D. Thirumalai, . J. Phys. Chem. B 110, 26403 (2006) Dynamic competition between catch and slip bonds in selectins bound to ligands. [151] C. Zhu, T. Yago, J.Z. Lou, V.I. Zarnitsyna, R.P. McEver, Ann. Biomed. Eng. 36, 604 (2008). Mechanisms for Flow-Enhanced Cell Adhesion. 129 [152] K.E. Caputo, D. Lee, M.R. King, D.A. Hammer, Biophys. J. 92, 787 (2007). Adhesive dynamics simulations of the shear threshold effect for leukocytes. [153] C.D. Paschall, W.H. Guilford, M.B. Lawrence, Biophys.J. 94, 1034 (2008). Enhancement of L-selectin, but not P-selectin, bond formation frequency by convective flow. [154] V. Vogel and M. Sheetz, Nat. Rev. Mol. Cell Biol. 7, 265 (2006). Local force and geometry sensing regulate cell functions. 130 [...]... structure of the cell, anchoring organelles and serving as structural components of the nuclear lamina and sarcomeres They also participate in cell- cell and cell- matrix adhesive junctions 2.2 Basics of Cell Adhesion In biological systems, cell adhesion is an integrated process involving multiple complex events which are regulated by complicated mechanisms and are highly interconnected Cell adhesion. .. cooperative behavior of the multiple-bond system remains to be explored 1.2 Thesis Contributions With an aim to develop a better understanding of the mechanics and kinetics of cell adhesion and detachment, this thesis presents three major contributions, namely: 1 Development of a cell system model to explain the rich kinetic phenomena of the cell adhesion process 1 Formulation of a numerical model... binding of cytoskeletons [67] The lateral diffusion of receptor proteins affects numerous membrane-involved activities such as receptor-mediated endocytosis, cell migration, and cell- cell and cell- ECM adhesions In the case of adhesion, the lateral mobility of receptors determines the speed at which receptors move towards their corresponding ligands, the rate at which they aggregate with each other, and. .. and accuracy of the commonly used Biomembrane Force Probe (BFP) technique 5 1 Analysis through numerical computations examining the cooperative effect of catch-slip mechanism on the decohesion of multiple-bond systems 1.3 Thesis Outline and Overview Chapter 2 provides an introduction of the background knowledge of cell adhesion This includes the structures and functions of cell, the manifestation and. .. uncontrolled flow of water The membrane is made more complex by the embedded protein molecules, which act as channels and 9 pumps that move different molecules into and out of the cell Besides supporting and retaining the cytoplasm, and being a selective barrier, cell membrane is also involved in cell communication and signaling via a special kind of proteins, the so-called receptors Moreover, many of the proteins... generate the forces used in cellular contraction and basic cell movements They also enable a dividing cell to pinch off into two 11 cells and are involved in amoeboid movements of certain types of cells The final group of filamentous proteins, the intermediate filaments, is around 10 nanometers in diameter There are some basic distinctions between intermediate filaments and the previous two cytoskeletal... of the force resolution of single-molecule biophysics BFP was originally developed by Evans and co-workers [31] and further studied in [32, 33, 34] It has been frequently used to measure minuscule forces in various physical and biological applications, such as single-molecular studies of neutrophil adhesion [35-39], examination of cell membrane’s thickness and compressibility [40], and inspection of. .. bindings between receptors and ligands 2.2.2 Specific Interactions Cells detect and interact with their extracellular environment through adhesion receptors, a variety of proteins or glycoprotein macromolecules embedded in the membrane Most of these receptors are comprised of three sections: the intracellular parts which are linked to cytoskeletons, the transmembrane part, and the extracellular part The transmembrane... membrane-bound nucleus and organelles, which are absent in prokaryotic cells A cell cannot survive if it is totally isolated from its environment; therefore, the cell membrane is selectively permeable, regulating the movement of water, nutrients and wastes into and out of the cell [2] As demonstrated in Figure 2.2, cell membrane includes two major building blocks: lipid (about 40% of the membrane) and protein... to the next ones, rendering a cascade of failure So the final lifetime of the cluster is an accumulation of the rupture time of each bond This zipper-like feature was observed in the unfolding of lg domains along native titin [87] 2.5 Modeling and Simulation Methods The biophysical study has greatly enriched the insights into the kinetics and mechanics of cell adhesion In addition to the biomimetic . MODELING AND SIMULATION OF CELL ADHESION AND DETACHMENT SUN LU NATIONAL UNIVERSITY OF SINGAPORE 2011 MODELING AND SIMULATION OF CELL ADHESION AND DETACHMENT. to provide in-depth understanding of the mechanics and kinetics of cell adhesion and detachment through biophysical modeling and computer simulation on intercellular interactions. We present. develop a better understanding of the mechanics and kinetics of cell adhesion and detachment, this thesis presents three major contributions, namely: 1 Development of a cell system model to