Actomyosin Controls Planarity and Folding of Epithelia in Response to Compression
T.P.J. Wyatt, J. Fouchard, A. Lisica, N. Khalilgharibi, B. Baum, P. Recho, A.J. Kabla, G.T. Charras
Nature Materials 19(1):109-117 (2020)
Abstract
Throughout embryonic development and adult life, epithelia are subjected to compressive deformations. While these have been shown to trigger mechanosensitive responses such as cell extrusion and differentiation, which span tens of minutes, little is known about how epithelia adapt to compression over shorter timescales. Here, using suspended epithelia, we uncover the immediate response of epithelial tissues to the application of in-plane compressive strains (5-80%). We show that fast compression induces tissue buckling followed by actomyosin-dependent tissue flattening that erases the buckle within tens of seconds, in both mono- and multi-layered epithelia. Strikingly, we identify a well-defined limit to this response, so that stable folds form in the tissue when compressive strains exceed a ‘buckling threshold’ of ~35%. A combination of experiment and modelling shows that this behaviour is orchestrated by adaptation of the actomyosin cytoskeleton as it re-establishes tissue tension following compression. Thus, tissue pre-tension allows epithelia to both buffer against deformation and sets their ability to form and retain folds during morphogenesis.
Figure sample
a, Schematic diagram showing the method for application of compressive strain to suspended epithelia. (i), Top view of the mechanical manipulation device. Uniaxial strain is applied to the tissue (green) by displacing the flexible arm. (ii),(iii), Profile views of the setup along the dashed line in (i): an epithelium (green) is suspended between two coverslips (black) (ii) and the right-hand coverslip is displaced, deforming the tissue (iii). The yellow lines denote the distance between the coverslips from which the applied ‘device strain’ is calculated. The blue dotted lines denote the tissue contour length. b, Time series of profiles of epithelia before and during application of various compressive strains ε, applied at different rates. Strain was applied either as a step at high strain rate (500% s−1, (i),(ii) and (iv),(v)) or as a ramp at low strain rate (0.5 % s−1, (iii),(vi)): step of intermediate amplitude (−35%) (i); step of large amplitude (−50%) (ii) and strain ramp (−80%) (iii), applied to MDCK monolayers. (iv)–(vi), As in (i)–(iii) but for multi-layered HaCaT epithelia. Cell membranes are marked with CellMask (green), the medium is visualized using dextran Alexa-647 (red) making coverslips appear dark by dye exclusion. Scale bars, 20 μm. The number n of biologically independent repeats of the representative images and the corresponding data in c,d,f is n = 17, 26, 8, 7, 10, 9, from (i)–(vi). c,d, Temporal evolution of the tissue strain (blue) of an MDCK monolayer after a step of −35% device strain (yellow) (c) and −50% device strain (d). e, Comparison of the buckling threshold εb in MDCK and HaCaT epithelia measured following a fast step or a slow ramp of compressive strain. NS, not significant, P = 0.45, 0.65 for MDCK and HaCaT, respectively; Mann–Whitney U-test. The distributions’ medians, first and third quartiles and ranges are represented by the central bars, bounding boxes and whiskers, respectively. The number of biologically independent experiments is given above each box plot. f, Temporal evolution of the tissue strain (blue) during a ramp of device strain (yellow). The dashed lines in d,f mark the maximum tissue strain, termed the buckling threshold εb.
