Force communication in multicellular tissues addressed by laser nanosurgery

Abstract

Cell contractility is a prominent mechanism driving multicellular tissue development and remodeling. Forces originated by the actomyosin cytoskeleton not only act within the cell body but can also propagate many layers away from the contraction source and grant tissues the ability to organize collectively and to achieve robust remodeling through development. Tissue tension is being thoroughly investigated in model organisms and increasing evidence is revealing the major role played by the communication, dynamics and propagation of cell-to-cell physical forces in multicellular remodeling. Recently, pulsed-laser-based surgery has fostered in vivo experimental studies to investigate intracellular and supracellular forces in action. The technique offers a unique method to perturb mechanical equilibrium in a subpopulation of cells or in a single cell, while the overall tissue remains intact. In particular, improved ablation precision with short laser pulses and the combination of this technique with biophysical models now allow an in-depth understanding of the role of cellular mechanics in tissue morphogenesis. We first characterize laser ablation modes available to perform intracellular, cellular, or multi-cellular ablation via the example of the model monolayer tissue of the amnioserosa of Drosophila by relating subnanosecond laser pulse energy to ablation efficiency and the probability of cavitation bubble formation. We then review recent laser nanosurgery experiments that have been performed in cultured cells and that tackle actomyosin mechanics and provide molecular insights into force-sensing mechanisms. We finally review studies showing the central role of laser ablation in revealing the nature and orientation of forces involved in intracellular contractility and force mechanosensing in tissue development, e.g., axis elongation, branching morphogenesis, or tissue invagination. We discuss the perspectives offered by the technique in force-based cell-cell communication and mechanosensing pathways.