Large deformation of living cells using laser traps

We present experimental results of large deformation of human red blood cells subjected to direct stretching by optical tweezers. The maximum external force imposed on the cell is in excess of 400 pN. A three-dimensional computational simulation of the biconcave cell membrane is also performed to extract the large deformation elastic properties from the experimental results obtained during loading as well as upon relaxation of the load. Different constitutive formulations of the cell membrane with its underlying spectrin network are explored in the computational simulations in an attempt to investigate the mechanical response and to compare the results so obtained with those derived from other independent experimental techniques. These results demonstrate new capabilities in the use of optical tweezers for study of cell deformation at large strains and provide a framework to explore possible effects of different loading configurations, disease states, chemical factors and environment on the large deformation characteristics of biological cells.

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

[2]  J. C. Simo,et al.  Remarks on rate constitutive equations for finite deformation problems: computational implications , 1984 .

[3]  S. Hénon,et al.  A new determination of the shear modulus of the human erythrocyte membrane using optical tweezers. , 1999, Biophysical journal.

[4]  R. Hochmuth,et al.  Red cell extensional recovery and the determination of membrane viscosity. , 1979, Biophysical journal.

[5]  S. Cowin,et al.  Biomechanics: Mechanical Properties of Living Tissues, 2nd ed. , 1994 .

[6]  R M Hochmuth,et al.  Erythrocyte membrane elasticity and viscosity. , 1987, Annual review of physiology.

[7]  C. P. Winlove,et al.  The deformation of spherical vesicles with permeable, constant-area membranes: application to the red blood cell. , 1999, Biophysical journal.

[8]  A. Cowman,et al.  Contribution of parasite proteins to altered mechanical properties of malaria-infected red blood cells. , 2002, Blood.

[9]  A C BURTON,et al.  MECHANICAL PROPERTIES OF THE RED CELL MEMBRANE. I. MEMBRANE STIFFNESS AND INTRACELLULAR PRESSURE. , 1964, Biophysical journal.

[10]  Shu Chien,et al.  Handbook of Bioengineering , 1986 .

[11]  C. Rotsch,et al.  Dimensional and mechanical dynamics of active and stable edges in motile fibroblasts investigated by using atomic force microscopy. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  S. Smith,et al.  Complete unfolding of the titin molecule under external force. , 1998, Journal of structural biology.

[13]  C. Lim,et al.  Mechanics of the human red blood cell deformed by optical tweezers , 2003 .

[14]  Y. Fung,et al.  Biomechanics: Mechanical Properties of Living Tissues , 1981 .

[15]  Y. C. Fung,et al.  Improved measurements of the erythrocyte geometry. , 1972, Microvascular research.

[16]  R M Hochmuth,et al.  Membrane viscoelasticity. , 1976, Biophysical journal.

[17]  S Chien,et al.  Theoretical and experimental studies on viscoelastic properties of erythrocyte membrane. , 1978, Biophysical journal.

[18]  M. Lavin Postreplication repair in mammalian cells after ultraviolet irradiation: a model. , 1978, Biophysical journal.

[19]  E. Evans,et al.  New membrane concept applied to the analysis of fluid shear- and micropipette-deformed red blood cells. , 1973, Biophysical journal.

[20]  D. Discher,et al.  Kinematics of red cell aspiration by fluorescence-imaged microdeformation. , 1996, Biophysical journal.

[21]  R. Mukhopadhyay,et al.  Stomatocyte–discocyte–echinocyte sequence of the human red blood cell: Evidence for the bilayer– couple hypothesis from membrane mechanics , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[22]  R M Hochmuth,et al.  Measurement of the elastic modulus for red cell membrane using a fluid mechanical technique. , 1973, Biophysical journal.

[23]  Michael P. Sheetz,et al.  Laser tweezers in cell biology , 1998 .

[24]  D. Boal,et al.  Simulations of the erythrocyte cytoskeleton at large deformation. I. Microscopic models. , 1998, Biophysical journal.

[25]  D. Boal,et al.  Mechanics of the cell , 2001 .

[26]  R. Simmons,et al.  Elasticity of the red cell membrane and its relation to hemolytic disorders: an optical tweezers study. , 1999, Biophysical journal.

[27]  K. Svoboda,et al.  Biological applications of optical forces. , 1994, Annual review of biophysics and biomolecular structure.

[28]  J. Simeon,et al.  Direct measurement of the area expansion and shear moduli of the human red blood cell membrane skeleton. , 2001, Biophysical journal.

[29]  S Chien,et al.  Elastic deformations of red blood cells. , 1977, Journal of Biomechanics.