living under stretch : from single cells to tissue – LuSt

Living organisms are sensitive to the mechanical environment and adapt their activity in response to solicitations. Specifically, embryogenesis involves dynamical changes that create the physical shape of the embryo, which show both as individual cell movements and collective cell rearrangements. Thus, a complete understanding of the role of forces on living organisms and tissue development requires a quantitative investigation both at the scale of the single cell and at the scale of the whole tissue. At the single cell scale there have been significant quantitative studies on the response mechanisms to solicitation, which have succeeded by means of a multidisciplinary approach combining physics and biology. In contrast, quantitative studies of such mechanisms at the tissue scale remain scarce. The present project is a quantitative biophysics study of how cells sense and exert force and strain in the context of developmental biology. We will investigate the different relevant scales, starting from the basic cellular scale and moving up to investigate multicellular rearrangements at the tissue scale.

In order to understand both the physically and biologically relevant questions, an experimental investigation of cellular response to deformation must produce quantitative and statistical significant information. In order to accomplish this, we will develop a new, fully automatized stretching apparatus, which will allow us to efficiently make a large number of simultaneous observations. To understand the key aspects of tissue mechanics, we will apply the apparatus to a model system consisting of a minimal cell junction. Such model system is simple enough for quantitative observation, yet it retains the key ingredients of tissue mechanics, both at the intracellular scale (cytoskeletal response) and at the intercellular scale (cell reorganization).

The project will follow a bottom-up approach through three relevant scales: the single cell, the cell junction, and the tissue. At each scale, we will apply our new stretching apparatus to investigate both the mechanical response and the involved biological players on the mechanotransduction pathways. At the single-cell level we will study the cell-shape changes under deformation, the cytoskeletal reorganization and the key molecular players in the acto-myosin response, and the role of membrane tension. At the intermediate cell junction scale, we will investigate the statics and dynamics of a cellular T1 transition, and we will determine the role of the cytoskeleton and of the cadherin adhesion complex in the reorganization dynamics. Finally, we will apply the previously acquired knowledge to the tissue scale in order to address a fundamental open question: how does the mechanical response at the tissue scale, characterized by the Young modulus and an effective viscosity, relate to the biological and mechanical responses at the cell scale (cell rearrangement, cytoskeletal reorganization)? Our project will yield valuable insight into this key biophysical question.