title: Growth-induced buckling of an epithelial layer.
abstract: We use a proof-of-concept experiment and two mathematical models to explore growth-induced tissue buckling, as may occur in colorectal crypt formation. Our experiment reveals how growth of a cultured epithelial monolayer on a thin flexible substrate can cause out-of-plane substrate deflections. We describe this system theoretically using a 'bilayer' model in which a growing cell layer adheres to a thin compressible elastic beam. We compare this with the 'supported-monolayer' model due to Edwards and Chapman (Bull Math Biol 69:1927-1942, 2007) for an incompressible expanding beam (representing crypt epithelium), which incorporates viscoelastic tethering to underlying stroma. We show that the bilayer model can exhibit buckling via parametric growth (in which the system passes through a sequence of equilibrium states, parameterised by the total beam length); in this case, non-uniformities in cell growth and variations in cell-substrate adhesion are predicted to have minimal effect on the shape of resulting buckled states. The supported-monolayer model reveals how competition between lateral supports and stromal adhesion influences the wavelength of buckled states (in parametric growth), and how non-equilibrium relaxation of tethering forces influences post-buckled shapes. This model also predicts that non-uniformities in growth patterns have a much weaker influence on buckled shapes than non-uniformities in material properties. Together, the experiment and models support the concept of patterning by growth-induced buckling and suggest that targeted softening of a growing cell layer provides greater control in shaping tissues than non-uniform growth.
authors.affiliation: School of Mathematical Sciences, University of Nottingham, Nottingham, NG7 2RD, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Nelson
authors.forename: D
authors.initials: D
authors.lastname: Howard
authors.forename: O E
authors.initials: OE
authors.lastname: Jensen
authors.forename: J R
authors.initials: JR
authors.lastname: King
authors.forename: F R A J
authors.initials: FR
authors.lastname: Rose
authors.forename: S L
authors.initials: SL
authors.lastname: Waters
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D002448:Cell Adhesion; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium / Q000254:growth & development*; D006801:Humans; D008567:Membranes, Artificial; D008954:Models, Biological; D051381:Rats; D013314:Stress, Mechanical
chemical_list: D008567:Membranes, Artificial