In vivo quantification of spatially varying mechanical properties in developing tissues

Abstract

It is generally believed that the mechanical properties of the cellular microenvironment and their spatiotemporal variations play a central role in sculpting embryonic tissues, maintaining organ architecture and controlling cell behavior, including cell differentiation. However, no direct in vivo and in situ measurement of mechanical properties within developing 3D tissues and organs has been performed yet. Here we introduce a technique that employs biocompatible ferrofluid microdroplets as local mechanical actuators and allows quantitative spatiotemporal measurements of mechanical properties in vivo. Using this technique, we show that vertebrate body elongation entails spatially-varying tissue mechanics along the anteroposterior axis. Specifically, we find that the zebrafish tailbud is viscoelastic (elastic below a few seconds and fluid after just one minute) and displays decreasing stiffness and increasing fluidity towards its posterior elongating region. This method opens new avenues to study mechanobiology in vivo, both in embryogenesis and in disease processes, including cancer.

Patterned Disordered Cell Motion Ensures Vertebral Column Symmetry

“…This hypothesis is supported by recent in vivo measurements in zebrafish using oil microdroplets. This study found the PSM is more viscous and has a higher elastic modulus than the PZ (Serwane et al, 2017). Importantly, the solidifying columns of paraxial mesoderm are responsible for advancing the posterior growth of the embryo (Dray et al, 2013; Zhou et al, 2009; Zhou et al, 2010; Zhou et al, 2015).…”

“…Future experiments examining other cell adhesion molecules, cell polarity and cytoskeletal tension will determine whether these cell biological properties are regulated at this transition and how these local cell biological processes give rise to tissue biomechanics. For example, quantification of in vivo tissue viscosity found that PZ domain is more fluid in cadherin 2 mutants (Serwane et al, 2017). More broadly, symmetry maintenance entails the cross-scale emergence of organism-level order from regulated disorder at the cellular level.…”

Tissue rheology in embryonic organization

“…The major limitation of this method is that it is difficult to decouple surface from deep cell/tissue properties. Ferrofluid oil Droplets (FDs): FDs are inserted between the cells of a tissue, and their initial spherical shape is deformed generating a local force dipole upon the application of an external uniform directional magnetic field (Serwane et al, 2017). A visible or monochromatic laser light is scattered upon interaction with acoustic waves that are spontaneously induced by density fluctuations within a sample (phonons, microscopic sounds waves).…”

Mechanical Stimulation of Cells Through Scaffold Design for Tissue Engineering

“…Another study employed magnetically responsive ferroluid microdroplets to measure local mechanical properties in developing embryos. Their results suggested that tissue mechanics might play a critical role in morphogenesis [39].…”