Mechanical instabilities and dynamics of living matter. From single-cell motility to collective cell migration

• Autores: Carles Blanch Mercader
• Directores de la Tesis: Jaume Casademunt i Viader (dir. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2015
• Idioma: inglés
• Tribunal Calificador de la Tesis: Jacques Prost (presid.), Xavier Trepat Guixer (secret.), Markus Bär (voc.)
• Materias:
  • Física
    • Mecánica
      • Mecánica de medios continuos
    • Física del estado sólido
      • Interfases
  • Ciencias de la vida
    • Biofísica
    • Biología celular
• Enlaces
  • Tesis en acceso abierto en:  TDX  Dipòsit Digital de la UB 
• Resumen

  • The thesis belongs to the field of biophysicis, in particular we evaluate from a physicial perspective biological processes that occur at the celular and multicelular scales involving collective phenomena of self-organization. Our modelling approach is based on the formalism of the active gels theory. Similarly as living systems, an ideal active gel is intrinsically out of equilibrium, due to its capacity to consume chemical energy. Within a certain range of validity the cells, the cytoskeleton, the tissues or even schools of fishes are expected to satisfy the same material properties as an active gel. This approach, coarse grain the systems by assuming that the large-scale and long-time limits are well described by a limited number of continuum fields, like the density of cells or the velocity of actin monomers. We apply this formalism to three main topics: self-locomotion of lamellar fragments, free-expansion of an epithelial monolayers, and the morphodynamics of the wing disk of the Drosophila melanogaster. In the first topic, we show that actin lamellar fragments driven solely by polymerisation forces at the bounding membrane are generically motile when the circular symmetry is spontaneously broken, with no need of molecular motors or global polarisation. We base our study on a nonlinear analysis of a recently introduced minimal model for an actin lamellar fragment. We prove the nonlinear instability of the center of mass and find an exact and simple relation between shape and center-of-mass velocity. A complex subcritical bifurcation scenario into traveling solutions is unfolded, where finite velocities appear through a nonadiabatic mechanism. In the second topic, we study the collective cell migration occurring in expanding cohesive epithelial cell sheets. This process involves the coordination of single cell traction forces, which are mechanically transmitted to adjacent neighbours via cell-cell junctions. The maps of reactive intracellular forces display a complex and heterogeneous spatio-temporal distribution, and are directly compared with the analytical stress and velocity profiles, so that we are able to track the temporal variations of the active celular traction force, the nematic correlation length and the effective viscosity at ultra-slow time scales. Furthermore, we generalise the previous biophysical model by incorporating a more realistic description of the material properties of an active gel. In particular, we include active stresses originated in part from the interaction between myosin motors and the intertwined actin meshwork within epithelial cells. We unveil a transition into an oscillatory periodic pattern. Interestingly, the complex material properties of an active gel allows to sustain elastic waves, even if the passive rheology is viscous-like. We classify in a phase-diagram the nonlinear assymptotic steady profiles, showing a rich variety of phenomenology. In the third topic, we study and classify the time-dependent morphologies of polarised tissues subjected to anisotropic but spatially homogeneous growth. Extending previous studies, we model the tissue as a fluid, and discuss the interplay of the active stresses generated by the anisotropic cell division and three types of passive mechanical forces: viscous stresses, friction with the environment and tension at the tissue boundary. The morphology dynamics is formulated as a free-boundary problem, and conformal mapping techniques are used to solve the evolution numerically. We elucidate how the different passive forces compete with the active stresses to shape the tissue in different temporal regimes and derive the corresponding scaling laws. We show that in general the aspect ratio of elongated tissues is non-monotonic in time, eventually recovering isotropic shapes in the presence of friction forces, which are asymptotically dominant.