Understanding how cells control their shape is an important scientific goal, since cells in our body constantly need to undergo shape changes to perform vital tasks such as growth and division. Conversely, abnormal cell shape changes contribute to life-threatening diseases such as cancer and developmental disorders. I propose to resolve the physical basis of active cell shape control by studying minimal cells built from purified cellular components. The main determinant of cell shape in animals is the actin cortex beneath the cell membrane, which contains molecular motors that actively generate forces. There is growing evidence that cells tightly balance these active forces with passive forces arising from cortex-membrane adhesion and elasticity. However, it is unclear how these forces are generated and controlled on the molecular level given the enormous complexity of cells. To circumvent this complexity, we will reconstitute cell-free actin networks and couple them to model biomembranes with the essential cellular linker protein septin. Using various advanced microscopy techniques, we will study (1) how active cortical networks and lipid bilayers influence each other’s spatial organization; (2) how active cortical networks control membrane shape; and (3) how spatial gradients in cortex contractility can cause cell shape polarization. My long-term ambition is to bridge the gap between the physical properties of cell-free model systems and biological functions in living cells. Thanks to recent breakthroughs in our understanding of the biophysical properties of contractile actin networks, we can now build more relevant cell-free model systems that can mimic active cell shape changes. To test the biological relevance of our findings, we will confront our results with live cell observations in fly embryos, together with a developmental biology group. Ultimately, the model cells developed here will enable a wide range of further studies of cellular (mal)functions.
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