CELLULAR TENSEGRITY MODELS AND CELL-SUBSTRATE INTERACTIONS

Mammalian cells control their shape and function by altering their mechanical properties through structural rearrangements and changes in molecular biochemistry at the nanometer scale. Yet, little is known about the molecular and biophysical basis of cell mechanics. Most of the existing engineering models of cells are ad hoc descriptions based on measurements obtained under particular experimental conditions, and these continuum models usually ignore contributions of subcellular structures and molecular components. More than 20 years ago, we introduced an alternative model of the cell based on tensegrity architecture which proposes that isometric tension in the cytoskeleton is critical for cell shape stability. Key to this model is the concept that this stabilizing tensile “prestress” results from a complementary force balance between multiple, discrete, molecular support elements, including microfilaments, intermediate filaments and microtubules in the cytoskeleton, as well as external adhesions to extracellular matrix and to neighboring cells. In this chapter, we review progress in the area of cellular tensegrity, including development of theoretical formulations of the tensegrity model that have led to multiple a priori predictions relating to both static and dynamic cell mechanical behaviors that have now been confirmed in experimental studies with living cells. We describe how the cytoskeleton and extracellular matrix form a single, tensionally integrated structural system as predicted by tensegrity, and how distinct molecular biopolymers (e.g., microfilaments vs microtubules) may bear either tensile or compressive loads inside the cell. The tensegrity model is also compared and contrasted with other models of cell mechanics. Taken together, these recent theoretical and experimental studies confirm that the cellular tensegrity model is a useful model because it provides a mechanism to link mechanics to structure at the molecular level, in addition to helping to explain how mechanical signals are transduced into biochemical responses within living cells and tissues.

[1]  Ben Fabry,et al.  Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells. , 2003, American journal of physiology. Cell physiology.

[2]  K Y Volokh,et al.  Tensegrity architecture explains linear stiffening and predicts softening of living cells. , 2000, Journal of biomechanics.

[3]  C. Turner,et al.  Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. , 1988, Annual review of cell biology.

[4]  C F Dewey,et al.  Theoretical estimates of mechanical properties of the endothelial cell cytoskeleton. , 1996, Biophysical journal.

[5]  J J Fredberg,et al.  Perturbed equilibria of myosin binding in airway smooth muscle: bond-length distributions, mechanics, and ATP metabolism. , 2000, Biophysical journal.

[6]  Ning Wang,et al.  Is cytoskeletal tension a major determinant of cell deformability in adherent endothelial cells? , 1998, American journal of physiology. Cell physiology.

[7]  Dimitrije Stamenović,et al.  A prestressed cable network model of the adherent cell cytoskeleton. , 2003, Biophysical journal.

[8]  D. Ingber The architecture of life. , 1998, Scientific American.

[9]  S. Gunst,et al.  Actin polymerization stimulated by contractile activation regulates force development in canine tracheal smooth muscle , 1999, The Journal of physiology.

[10]  B. Helmke,et al.  Mapping mechanical strain of an endogenous cytoskeletal network in living endothelial cells. , 2003, Biophysical journal.

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

[12]  Dimitrije Stamenović,et al.  Cell prestress. II. Contribution of microtubules. , 2002, American journal of physiology. Cell physiology.

[13]  D. Ingber,et al.  Altering the cellular mechanical force balance results in integrated changes in cell, cytoskeletal and nuclear shape. , 1992, Journal of cell science.

[14]  J J Fredberg,et al.  Pharmacological activation changes stiffness of cultured human airway smooth muscle cells. , 1996, The American journal of physiology.

[15]  Ning Wang,et al.  Cell spreading controls balance of prestress by microtubules and extracellular matrix. , 2004, Frontiers in bioscience : a journal and virtual library.

[16]  M. Dembo,et al.  Stresses at the cell-to-substrate interface during locomotion of fibroblasts. , 1999, Biophysical journal.

[17]  D E Ingber,et al.  Cooperative control of Akt phosphorylation, bcl-2 expression, and apoptosis by cytoskeletal microfilaments and microtubules in capillary endothelial cells. , 2001, Molecular biology of the cell.

[18]  Christian Oddou,et al.  A cellular tensegrity model to analyse the structural viscoelasticity of the cytoskeleton. , 2002, Journal of theoretical biology.

[19]  Daniel Isabey,et al.  Assessment of mechanical properties of adherent living cells by bead micromanipulation: comparison of magnetic twisting cytometry vs optical tweezers. , 2002, Journal of biomechanical engineering.

[20]  E. Salmon,et al.  Actomyosin-based Retrograde Flow of Microtubules in the Lamella of Migrating Epithelial Cells Influences Microtubule Dynamic Instability and Turnover and Is Associated with Microtubule Breakage and Treadmilling , 1997, The Journal of cell biology.

[21]  D E Ingber,et al.  Cytoskeletal filament assembly and the control of cell spreading and function by extracellular matrix. , 1995, Journal of cell science.

[22]  Ning Wang,et al.  Caldesmon-dependent switching between capillary endothelial cell growth and apoptosis through modulation of cell shape and contractility , 2004, Angiogenesis.

[23]  S. Kaech,et al.  Cytoskeletal Plasticity in Cells Expressing Neuronal Microtubule-Associated Proteins , 1996, Neuron.

[24]  D Stamenović,et al.  A microstructural approach to cytoskeletal mechanics based on tensegrity. , 1996, Journal of theoretical biology.

[25]  D. Wirtz,et al.  Mechanics of living cells measured by laser tracking microrheology. , 2000, Biophysical journal.

[26]  R. Paul,et al.  Effects of microtubule disruption on force, velocity, stiffness and [Ca(2+)](i) in porcine coronary arteries. , 2000, American journal of physiology. Heart and circulatory physiology.

[27]  Jill U. Adams Gains in pain research , 2003 .

[28]  A. Harris,et al.  Silicone rubber substrata: a new wrinkle in the study of cell locomotion. , 1980, Science.

[29]  D Stamenović,et al.  Contribution of intermediate filaments to cell stiffness, stiffening, and growth. , 2000, American journal of physiology. Cell physiology.

[30]  E. Elson,et al.  Contraction due to microtubule disruption is associated with increased phosphorylation of myosin regulatory light chain. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[31]  R M Nerem,et al.  Application of the micropipette technique to the measurement of cultured porcine aortic endothelial cell viscoelastic properties. , 1990, Journal of biomechanical engineering.

[32]  Y. Wang,et al.  Cell locomotion and focal adhesions are regulated by substrate flexibility. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[33]  D. Ingber,et al.  Role of RhoA, mDia, and ROCK in Cell Shape-dependent Control of the Skp2-p27kip1 Pathway and the G1/S Transition* , 2004, Journal of Biological Chemistry.

[34]  Rheological constitutive equation for a model of soft glassy materials , 1997, cond-mat/9712001.

[35]  G. Forgacs On the possible role of cytoskeletal filamentous networks in intracellular signaling: an approach based on percolation. , 1995, Journal of cell science.

[36]  C. S. Chen,et al.  Geometric control of cell life and death. , 1997, Science.

[37]  D. Ingber,et al.  Mechanotransduction: All Signals Point to Cytoskeleton, Matrix, and Integrins , 2002, Science's STKE.

[38]  Donald E Ingber,et al.  Mechanical properties of individual focal adhesions probed with a magnetic microneedle. , 2004, Biochemical and biophysical research communications.

[39]  C. S. Chen,et al.  Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[40]  D E Ingber,et al.  Role of basal lamina in neoplastic disorganization of tissue architecture. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[41]  D Stamenović,et al.  A tensegrity model of the cytoskeleton in spread and round cells. , 1998, Journal of biomechanical engineering.

[42]  Ning Wang,et al.  Regulation of cytoskeletal mechanics and cell growth by myosin light chain phosphorylation. , 1998, American journal of physiology. Cell physiology.

[43]  D. Ingber,et al.  A Computational Tensegrity Model Predicts Dynamic Rheological Behaviors in Living Cells , 2004, Annals of Biomedical Engineering.

[44]  N. B. Brookes,et al.  Spin-Orbit Coupling in the Mott Insulator Ca2RuO4 , 2001 .

[45]  M S Kolodney,et al.  Isometric contraction by fibroblasts and endothelial cells in tissue culture: a quantitative study , 1992, The Journal of cell biology.

[46]  P. Davies,et al.  Flow-mediated endothelial mechanotransduction. , 1995, Physiological reviews.

[47]  Ning Wang,et al.  Distending stress of the cytoskeleton is a key determinant of cell rheological behavior. , 2004, Biochemical and biophysical research communications.

[48]  Denis Wirtz,et al.  Towards a regional approach to cell mechanics. , 2004, Trends in cell biology.

[49]  Donald E Ingber,et al.  Extracellular matrix controls myosin light chain phosphorylation and cell contractility through modulation of cell shape and cytoskeletal prestress. , 2004, American journal of physiology. Cell physiology.

[50]  J. Folkman,et al.  Role of cell shape in growth control , 1978, Nature.

[51]  M Radmacher,et al.  Measuring the elastic properties of biological samples with the AFM. , 1997, IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society.

[52]  Ning Wang,et al.  Effect of the cytoskeletal prestress on the mechanical impedance of cultured airway smooth muscle cells. , 2002, Journal of applied physiology.

[53]  Kenneth Snelson,et al.  Snelson On The Tensegrity Invention , 1996 .

[54]  D E Ingber,et al.  Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. , 1994, Biophysical journal.

[55]  J. Howard,et al.  Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape , 1993, The Journal of cell biology.

[56]  M. F. Coughlin,et al.  A Tensegrity Structure With Buckling Compression Elements: Application to Cell Mechanics , 1997 .

[57]  Dimitrije Stamenović,et al.  Microtubules may harden or soften cells, depending of the extent of cell distension. , 2005, Journal of biomechanics.

[58]  R. Connelly,et al.  Mathematics and Tensegrity , 1998, American Scientist.

[59]  A C Maggs,et al.  Analysis of microtubule rigidity using hydrodynamic flow and thermal fluctuations. , 1994, The Journal of biological chemistry.

[60]  D. Ingber Tensegrity: the architectural basis of cellular mechanotransduction. , 1997, Annual review of physiology.

[61]  D. Ingber,et al.  Mechanical behavior in living cells consistent with the tensegrity model , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[62]  Donald E. Ingber,et al.  The riddle of morphogenesis: A question of solution chemistry or molecular cell engineering? , 1993, Cell.

[63]  T. Stossel On the crawling of animal cells. , 1993, Science.

[64]  P. Janmey,et al.  Elasticity of semiflexible biopolymer networks. , 1995, Physical review letters.

[65]  D. Ingber,et al.  Opposing views on tensegrity as a structural framework for understanding cell mechanics. , 2000, Journal of applied physiology.

[66]  D. Ingber Tensegrity I. Cell structure and hierarchical systems biology , 2003, Journal of Cell Science.

[67]  G W Brodland,et al.  Intermediate filaments may prevent buckling of compressively loaded microtubules. , 1990, Journal of biomechanical engineering.

[68]  D. Navajas,et al.  Scaling the microrheology of living cells. , 2001, Physical review letters.

[69]  M. Sheetz,et al.  Cell migration: regulation of force on extracellular-matrix-integrin complexes. , 1998, Trends in cell biology.

[70]  Ning Wang,et al.  Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[71]  Ning Wang,et al.  Rheology of airway smooth muscle cells is associated with cytoskeletal contractile stress. , 2004, Journal of applied physiology.

[72]  D. Smith,et al.  Active fluidization of polymer networks through molecular motors , 2002, Nature.

[73]  Robert E. Buxbaum,et al.  Direct Observations of the Mechanical Behaviors of the Cytoskeleton in Living Fibroblasts , 1999, The Journal of cell biology.

[74]  N O Petersen,et al.  Dependence of locally measured cellular deformability on position on the cell, temperature, and cytochalasin B. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[75]  K. Jacobson,et al.  Local measurements of viscoelastic parameters of adherent cell surfaces by magnetic bead microrheometry. , 1998, Biophysical journal.

[76]  R. Nerem,et al.  Elongation of confluent endothelial cells in culture: the importance of fields of force in the associated alterations of their cytoskeletal structure. , 1995, Experimental cell research.

[77]  D Isabey,et al.  Stiffening response of a cellular tensegrity model. , 1999, Journal of theoretical biology.

[78]  D. Ingber,et al.  Mechanotransduction across the cell surface and through the cytoskeleton , 1993 .

[79]  J. McGarry,et al.  A three-dimensional finite element model of an adherent eukaryotic cell. , 2004, European cells & materials.

[80]  D. Ingber,et al.  Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts. , 1998, Journal of cell science.

[81]  D. Ingber Tensegrity II. How structural networks influence cellular information processing networks , 2003, Journal of Cell Science.

[82]  D. Ingber,et al.  Cellular tensegrity : defining new rules of biological design that govern the cytoskeleton , 2022 .

[83]  Jean Lai,et al.  Stiffness changes in cultured airway smooth muscle cells. , 2002, American journal of physiology. Cell physiology.

[84]  C. S. Chen,et al.  Control of cyclin D1, p27(Kip1), and cell cycle progression in human capillary endothelial cells by cell shape and cytoskeletal tension. , 1998, Molecular biology of the cell.

[85]  Daniel I. C. Wang,et al.  Engineering cell shape and function. , 1994, Science.

[86]  D. Boal,et al.  Simulations of the erythrocyte cytoskeleton at large deformation. II. Micropipette aspiration. , 1998, Biophysical journal.

[87]  D. Stamenović,et al.  Cell prestress. I. Stiffness and prestress are closely associated in adherent contractile cells. , 2002, American journal of physiology. Cell physiology.

[88]  Paul A. Janmey,et al.  Resemblance of actin-binding protein/actin gels to covalently crosslinked networks , 1990, Nature.