Statistical physics of active matter, cell division and cell aggregation

In these Lecture Notes we aim at clarifying how soft matter physics, and herein notably statistical mechanics and fluid mechanics, can be engaged to understand and manipulate non -equilibrium systems consisting of numerous (microscopic) constituents that convert (chemical) energy to mechanical energy, or vice versa, and that are known as active matter. Hydrody-namic theory, vitally extended to include (anisotropic) active stress, provides an astonishingly successful scaffold for tackling the problem of spontaneous flow in active nematics, all the way to active turbulence. The laws of physics, nonchalantly trespassing the border crossing between inanimate particle and living cell, are seen to perform cum laude in describing the bi-directional coupling between division and apoptosis on the one hand and mechanical stress on the other. Fluidization of cellular tissue by cell division is a conceptual leap in this arena. The active behavior of nematic tissues (cell extrusion, multilayer formation, ... ) turns out to be controlled by topological defects in the orientational order. Playgrounds by excellence for exhibiting stress -growth coupling are multicellular spheroids serving as model tumors, and cysts used as stem cell factories for cell therapy. Finally, our study of villi and crypts in the intestine furnishes a synthesis of various concepts explored. Cell mechanical pressure and cell layer geometrical curvature turn out to provide the dynamical ingredients which, when coupled to the cell division rate, allow one to develop a physical theory of tissue morphology which hopefully will have practical impact on cancer research.