Cells are the smallest autonomous building blocks of our body. Their shape and mechanics are governed by a delicate force balance between the plasma membrane and the cytoskeleton, an elastic scaffold of stiff protein filaments. The cytoskeleton mechanically stabilizes the thin and fragile lipid bilayer membrane but also actively drives changes in membrane shape by exerting pushing and pulling forces. A paradigmatic example of this mechanical interplay is the process of cell division, which is driven by a contractile ring of actin filaments that constricts the membrane mid-cell. The key structural component is a cross-linked network of actin filaments that is tightly anchored to the plasma membrane and constriction is driven by myosin motor molecules that utilize ATP to slide the actin filaments. Most research till now has focused on the question how force generation by the actin cytoskeleton changes membrane shape.
The aim of this project is to ask the reverse question: how does the membrane geometry determine the assembly and constriction of the actin ring? Models suggest that actomyosin ring formation and furrow ingression sensitively depend on the cell geometry and the balance between cortical tension at the cell equator and the poles. Some models predict that contractile ring initiation furthermore requires cooperation with lipids and proteins that promote membrane curvature. To experimentally test these ideas, you will reconstitute synthetic cells by encapsulating a minimal machinery required for actin ring assembly inside lipid vesicles and use microfluidic devices, optical tweezers, and curvature-inducing proteins to impose a controlled membrane geometry. To measure the dynamic response of the actin and the membrane, you will make extensive use of confocal fluorescence imaging, FCS, FRAP, and single-molecule imaging. This project is part of a large Dutch research initiative (www.Basyc.nl) aimed at building an autonomous self-reproducing synthetic cell. Our team’s contribution focuses on the mechanical machinery needed to achieve cell cleavage. Within the team, you will closely collaborate with three PhD students that work on several different aspects of the actin-based cell division machinery.
Tagged as: Engineering, Life Sciences, Physics
Postdoctoral Researcher, Modeling Gene Disruptions in Human Neurons A 3-year postdoctoral position on Modeling Gene Disruptions in Human Neurons is...Apply