All the cells in our body come from an initial spherical cell, the fertilised egg. As the embryo develops and its cells differentiate, they acquire distinct shapes. These shapes are part of a cell’s identity, are central to cellular function, and cell shape deregulation is at the heart of many pathologies including cancer. It is thus essential to understand how cell morphology is controlled in physiological and pathological conditions.
Understanding cell shape is a question at the interface of physics and biology. Indeed, cell morphology is the net result of mechanical forces acting on the cell membrane, both from the outside, through interaction with the environment, and from the inside, where the cellular cytoskeletal networks can push and pull on the membrane. Understanding cell shape control thus requires studies integrating biology with physics. The NanoMechShape project takes such a cross-disciplinary approach to investigate the regulation of animal cell shape.
In animal cells, intracellular forces controlling cell shape are mostly exerted by networks of actin and myosin, the same proteins that generate contractility in muscle cells. In non-muscle cells, they form networks supporting the cellular membrane and, by pushing and pulling on the membrane, drive cell deformations. The NanoMechShape focused on 3 core objectives:
1. To explore how the nanoscale organisation of cellular acto-myosin networks controls the mechanical properties of these networks.
2. To investigate how this nanoscale organisation changes to generate local forces driving cell division, where a cell forms a cleavage furrow to cut itself into two.
3. To understand how acto-myosin networks are reorganised when cells transition from rounded shapes towards spread shapes during cellular state changes.
Over the course of the project, we identified key molecular principles by which nanoscale interactions between actin and myosin regulate cell mechanics and cell shape change. We discovered that membrane tension in particular acts as a key signal controlling feedbacks between cell shape and cell state. Finally, we developed innovative imaging and computational tools to quantify cell-shape dynamics, and used them to uncover basic physical principles driving cell shape change. Together, these results establish a new multiscale understanding of how nanoscale organisation of cellular components determines cell mechanics, linking nanoscale structures to cell-scale behaviour.
