Effect of an osmotic stress on multicellular aggregates.

There is increasing evidence that multicellular structures respond to mechanical cues, such as the confinement and compression exerted by the surrounding environment. In order to understand the response of tissues to stress, we investigate the effect of an isotropic stress on different biological systems. The stress is generated using the osmotic pressure induced by a biocompatible polymer. We compare the response of multicellular spheroids, individual cells and matrigel to the same osmotic perturbation. Our findings indicate that the osmotic pressure occasioned by polymers acts on these systems like an isotropic mechanical stress. When submitted to this pressure, the volume of multicellular spheroids decreases much more than one could expect from the behavior of individual cells.

[1]  R. Rivlin Large elastic deformations of isotropic materials IV. further developments of the general theory , 1948, Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences.

[2]  R. Bonnecaze,et al.  Extracellular matrix stiffness and architecture govern intracellular rheology in cancer. , 2009, Biophysical journal.

[3]  J. Jardin,et al.  Casein micelle dispersions under osmotic stress. , 2009, Biophysical journal.

[4]  C. Murphy,et al.  The elastic modulus of Matrigel as determined by atomic force microscopy. , 2009, Journal of structural biology.

[5]  D. G. T. Strange,et al.  Extracellular-matrix tethering regulates stem-cell fate. , 2012, Nature materials.

[6]  Manuel Théry,et al.  A new micropatterning method of soft substrates reveals that different tumorigenic signals can promote or reduce cell contraction levels. , 2011, Lab on a chip.

[7]  B. Cabane,et al.  Osmotic pressure of latex dispersions , 1994 .

[8]  L. Kunz-Schughart,et al.  Multicellular tumor spheroids: an underestimated tool is catching up again. , 2010, Journal of biotechnology.

[9]  Manuel Théry,et al.  Cell shape and cell division. , 2006, Current opinion in cell biology.

[10]  Ivo F Sbalzarini,et al.  Dynamic measurement of the height and volume of migrating cells by a novel fluorescence microscopy technique. , 2011, Lab on a chip.

[11]  Nicolas Bremond,et al.  Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro , 2013, Proceedings of the National Academy of Sciences.

[12]  Triantafyllos Stylianopoulos,et al.  Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors , 2012, Proceedings of the National Academy of Sciences.

[13]  M. Mooney A Theory of Large Elastic Deformation , 1940 .

[14]  F. Guilak,et al.  Hyper-osmotic stress induces volume change and calcium transients in chondrocytes by transmembrane, phospholipid, and G-protein pathways. , 2001, Journal of biomechanics.

[15]  K. Strange,et al.  Cellular volume homeostasis. , 2004, Advances in physiology education.

[16]  D. W. Saunders,et al.  Large elastic deformations of isotropic materials VII. Experiments on the deformation of rubber , 1951, Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences.

[17]  Jacques Prost,et al.  Supplements to : Isotropic stress reduces cell proliferation in tumor spheroids , 2011 .

[18]  T C Fisher,et al.  The hydrodynamic radii of macromolecules and their effect on red blood cell aggregation. , 2004, Biophysical journal.

[19]  M. Dembo,et al.  Cell movement is guided by the rigidity of the substrate. , 2000, Biophysical journal.

[20]  Jacques Prost,et al.  Compressive stress inhibits proliferation in tumor spheroids through a volume limitation. , 2014, Biophysical journal.

[21]  Xavier Gidrol,et al.  Controlled 3D culture in Matrigel microbeads to analyze clonal acinar development. , 2015, Biomaterials.

[22]  Thomas Boudou,et al.  An extended relationship for the characterization of Young's modulus and Poisson's ratio of tunable polyacrylamide gels. , 2006, Biorheology.

[23]  R. Rivlin Large Elastic Deformations of Isotropic Materials , 1997 .

[24]  Laurent Malaquin,et al.  Stress clamp experiments on multicellular tumor spheroids. , 2011, Physical review letters.

[25]  Paolo A. Netti,et al.  Solid stress inhibits the growth of multicellular tumor spheroids , 1997, Nature Biotechnology.

[26]  Dimitri Debruyne,et al.  Precise determination of the Poisson ratio in soft materials with 2D digital image correlation , 2013 .

[27]  R. S. Rivlin,et al.  Large elastic deformations of isotropic materials VIII. Strain distribution around a hole in a sheet , 1951, Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences.

[28]  Frank Jülicher,et al.  Stress distributions and cell flows in a growing cell aggregate , 2014, Interface Focus.

[29]  Adam J Engler,et al.  Preparation of Hydrogel Substrates with Tunable Mechanical Properties , 2010, Current protocols in cell biology.

[30]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[31]  E. Geissler,et al.  The Poisson Ratio in Polymer Gels , 1980 .