Biological Tissues as Active Materials J.F. Joanny Physico-Chimie - PowerPoint PPT Presentation

Biological Tissues as Active Materials J.F. Joanny Physico-Chimie Curie Institut Curie Les Houches school on Active Matter, Les Houches September 2018 Joanny (Institut Curie) Tissues TAU 1 / 48

Multicellular spheroids Confluent monolayers Intestinal epithelia

Epithelial tissues Epithelial structure Dividing cells Differentiated cells Apoptotic cells Tissue mechanics Solid-like behavior Liquid-like behavior Viscoelastic liquid, relaxation time T Plastic behavior Joanny (Institut Curie) Tissues TAU 3 / 48

Outline Homeostatic state of tissues 1 Joanny (Institut Curie) Tissues TAU 4 / 48

Outline Homeostatic state of tissues 1 Fluidization of tissues by cell division 2 Joanny (Institut Curie) Tissues TAU 4 / 48

Outline Homeostatic state of tissues 1 Fluidization of tissues by cell division 2 Tissues as active liquids 3 Defects in nematic tissue monolayers Spontaneous flow of tissues Joanny (Institut Curie) Tissues TAU 4 / 48

Outline Homeostatic state of tissues 1 Fluidization of tissues by cell division 2 Tissues as active liquids 3 Defects in nematic tissue monolayers Spontaneous flow of tissues Muticellular spheroids 4 Joanny (Institut Curie) Tissues TAU 4 / 48

Outline Homeostatic state of tissues 1 Fluidization of tissues by cell division 2 Tissues as active liquids 3 Defects in nematic tissue monolayers Spontaneous flow of tissues Muticellular spheroids 4 Epithelial tissues, Intestine 5 Vertex models of epithelial layers Intestine Joanny (Institut Curie) Tissues TAU 4 / 48

Outline Homeostatic state of tissues 1 Fluidization of tissues by cell division 2 Tissues as active liquids 3 Defects in nematic tissue monolayers Spontaneous flow of tissues Muticellular spheroids 4 Epithelial tissues, Intestine 5 Vertex models of epithelial layers Intestine Joanny (Institut Curie) Tissues TAU 5 / 48

Homeostatic Pressure Basan Permeable compartments Fluctuations due to cell divisions Joanny (Institut Curie) Tissues TAU 6 / 48

Possible measurements of homeostatic pressure F.Montel, D. Vijgnevic Tissue growth inside an agarose gel Helmlinger et al. Pressure ∼ 10 4 Pa Joanny (Institut Curie) Tissues TAU 7 / 48

Possible measurements of homeostatic pressure F.Montel, D. Vijgnevic Tissue growth inside an agarose gel Helmlinger et al. Pressure ∼ 10 4 Pa Semi-permeable membrane (dialysis bags) Cabane Tissue spheroids in micropipettes Guevorkian,Brochard PAA beads as microsensors G.Cappello et al. Joanny (Institut Curie) Tissues TAU 7 / 48

Possible measurements of homeostatic pressure F.Montel, D. Vijgnevic Tissue growth inside an agarose gel Helmlinger et al. Pressure ∼ 10 4 Pa Semi-permeable membrane (dialysis bags) Cabane Tissue spheroids in micropipettes Guevorkian,Brochard PAA beads as microsensors G.Cappello et al. 2-dimensional tissues Silberzan Stress measurement in a tissue O. Campas et al. Joanny (Institut Curie) Tissues TAU 7 / 48

Cell proliferation and stress Cheng et al. Joanny (Institut Curie) Tissues TAU 8 / 48

Possible measurements of homeostatic pressure F.Montel, D. Vijgnevic Tissue growth inside an agarose gel Helmlinger et al. Pressure ∼ 10 4 Pa Semi-permeable membrane (dialysis bags) Cabane Tissue spheroids in micropipettes Guevorkian,Brochard PAA beads as microsensors G.Cappello et al. Joanny (Institut Curie) Tissues TAU 9 / 48

PAA microsensors Joanny (Institut Curie) Tissues TAU 10 / 48

Possible measurements of homeostatic pressure F.Montel, D. Vijgnevic Tissue growth inside an agarose gel Helmlinger et al. Pressure ∼ 10 4 Pa Semi-permeable membrane (dialysis bags) Cabane Tissue spheroids in micropipettes Guevorkian,Brochard PAA beads as microsensors G.Cappello et al. 2-dimensional tissues Silberzan Stress measurement in a tissue O. Campas et al. Joanny (Institut Curie) Tissues TAU 11 / 48

Oils droplets Epithelial and mesenchymal cell Joanny (Institut Curie) Tissues TAU 12 / 48

Tissue Competition and sorting Joanny (Institut Curie) Tissues TAU 13 / 48

Outline Homeostatic state of tissues 1 Fluidization of tissues by cell division 2 Tissues as active liquids 3 Defects in nematic tissue monolayers Spontaneous flow of tissues Muticellular spheroids 4 Epithelial tissues, Intestine 5 Vertex models of epithelial layers Intestine Joanny (Institut Curie) Tissues TAU 14 / 48

Coupling between stress and cell division Cell division coupled to stress Fink, Cuvelier Fink, Cuvelier Joanny (Institut Curie) Tissues TAU 15 / 48

Cell diffusion Cell diffusion in an aggregate Division and apoptosis noise Cell conservation law d ρ dt = ρ ( k d − k a )( ρ ) − ρ v γγ + ξ ( t ) Correlation � ξ ( r , t ) ξ ( r ′ , t ′ ) � = ( k a + k d ) ρδ ( t − t ′ ) δ ( r − r ′ ) Diffusion constant proportional to k d if K / p ρ ≫ 1 Joanny (Institut Curie) Tissues TAU 16 / 48

Epiboly J. Ranft, T. Risler CP Heisenberg et al. Joanny (Institut Curie) Tissues TAU 17 / 48

Tissue simulations J. Elgeti, M. Basan Joanny (Institut Curie) Tissues TAU 18 / 48

Outline Homeostatic state of tissues 1 Fluidization of tissues by cell division 2 Tissues as active liquids 3 Defects in nematic tissue monolayers Spontaneous flow of tissues Muticellular spheroids 4 Epithelial tissues, Intestine 5 Vertex models of epithelial layers Intestine Joanny (Institut Curie) Tissues TAU 19 / 48

Confluent elongated cells G. Duclos, P. Silberzan Nematic order of Spindle shaped cells Spindle-shaped cells: NIH 3T3, RPE1, C2 C12 Elongated cells show nematic order: head-tail symmetry Different defects expected for polar and nematic cells Spontaneous cell flow due to activity Defect motion Joanny (Institut Curie) Tissues TAU 20 / 48

Defect motion in cell monolayers Only + 1 / 2 and − 1 / 2 defects Spontaneous motions of + 1 / 2 defects − 1 / 2 defects do not move Annihilation between + 1 / 2 and − 1 / 2 defects Joanny (Institut Curie) Tissues TAU 21 / 48

Cell Monolayers confined to a disk Defect relaxation Tangential boundary condition Relaxation to two + 1 / 2 defects Activity negligible Joanny (Institut Curie) Tissues TAU 22 / 48

Cell orientation in a confined disk C. Erlenkamper Free energy minimization 2 defects in a passive nematic disk. Ignore activity Minimize elastic energy with two defects at a radius r 0 � d x K 2 ( ∇ θ ) 2 F = Minimum of the free energy r 0 = 0 , 67 R Excellent agreement with experiment Effective temperature independent of R Joanny (Institut Curie) Tissues TAU 23 / 48

Spontaneous tissue flow G. Duclos, V. Yashunsky, P. Silberzan Experiment Stripe width 50 µ m to 800 µ m Cell orientation PIV Velocity and cell orientation Joanny (Institut Curie) Tissues TAU 24 / 48

Active gel theory C. Blanch-Mercader Spontaneous flow Fredericks transition Theoretical developments Substrate friction: screening length λ = ( η/ξ ) 1 / 2 Transverse flow related to cell division Chiral effects Joanny (Institut Curie) Tissues TAU 25 / 48

Outline Homeostatic state of tissues 1 Fluidization of tissues by cell division 2 Tissues as active liquids 3 Defects in nematic tissue monolayers Spontaneous flow of tissues Muticellular spheroids 4 Epithelial tissues, Intestine 5 Vertex models of epithelial layers Intestine Joanny (Institut Curie) Tissues TAU 26 / 48

Interfacial tension of a tissue Relaxation measurements Steinberg et al. Relaxation measurements Steinberg et al., F. Montel Neural Retina relaxation Liquid description Typical relaxation time τ a ∼ 100 s small compared to division rates σ αβ = 2 η ˜ Liquid limit ˜ v αβ Viscosity η = E τ a , Modulus E ∼ 1000 Pa Joanny (Institut Curie) Tissues TAU 27 / 48

Cortical tension Optical Imaging Electron microscopy Charras Medalia Actomyosin layer Dense actin layer Polymerization from the surface Thickness ∼ 1 µ m (formins) Filaments parallel to the cell Treadmilling time ∼ 30s surface Cortex tension Joanny (Institut Curie) Tissues TAU 28 / 48

Metastatic Inefficiency 0.14 0.08 0.12 Probability 0.06 0.04 0.1 Probability 0.02 n c  3 0.08 0 5 10 15 20 Time [d] 120 t  1 0 d Number of Tumors 100 0.06 n c  1 0 80 60 0.04 40 20 0.02 0 10 50 90 130 170 210 250 290 330 370 More Size Interval t  1 4 d 0 5 10 15 20 25 30 Critical Cell Number Joanny (Institut Curie) Tissues TAU 29 / 48

Spheroid growth F .Montel, M.Delarue Growth experiments Indirect experiments ◮ Dialysis bag ◮ Pressure exerted by dextran Direct experiments ◮ Spheroid in contact with dextran solutions ◮ No penetration of dextran in spheroid Joanny (Institut Curie) Tissues TAU 30 / 48

Surface growth Pressure dependence 2 / 3 ∂ t V = ( k d − k a ) V + 4 π ( 3 δ k s λ V 2 / 3 4 π ) Nutrient effect Elgeti Joanny (Institut Curie) Tissues TAU 31 / 48

Cell flow Injection of fluorescent nano-particles Incompressible fluid Velocity field ∇ · v = k ( r ) Joanny (Institut Curie) Tissues TAU 32 / 48