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Generation and biomechanical characterization of artificial actomyosin cortices in vitro
The complexity of biological materials is a major limiting factor for the discovery of the basic cues that govern the metastatic process. With this in mind, the selected student will participate in the development of an in vitro model of metastasizing cells.
The ability of tumor cells to invade adjacent tissues, extravasate and subsequently spread to distant sites of the body is the main cause of cancer lethality, with over 90% of cancer‐related deaths being directly attributable to metastatic dissemination. This process comprises multiple steps in different locations of the body, and therefore the metastatic cells are exposed to different microenvironments during their journey, including periods in which travel through blood in a free-floating state. Nevertheless, the complexity of biological materials and the enormous scope of their potential interaction is a major limiting factor for the discovery of the basic cues that govern these processes. With this in mind, the selected student will participate in the development of a highly versatile research tool that consists in the reconstitution of the eukaryotic actin-based machinery confined inside cell-sized lipidic vesicles, which mimic metastatic cells during their hematogenous dissemination. He will further use a recently developed method for the high-throughput mechanical analysis of free-floating particles and study the effect of the membrane and microenvironmental properties on the mechanical features of the resulting actomyosin cortex. Immunofluorescence and real-time imaging will be further used to characterize the actin networks.
Figure: Generation of actin networks (A) and cell-sized vesicles enclosing fluorescent proteins (B). Scale bars represents 2.5 μm in A and 5 μm in B.
The ability of tumor cells to invade adjacent tissues, extravasate and subsequently spread to distant sites of the body is the main cause of cancer lethality, with over 90% of cancer‐related deaths being directly attributable to metastatic dissemination. This process comprises multiple steps in different locations of the body, and therefore the metastatic cells are exposed to different microenvironments during their journey, including periods in which travel through blood in a free-floating state. Nevertheless, the complexity of biological materials and the enormous scope of their potential interaction is a major limiting factor for the discovery of the basic cues that govern these processes. With this in mind, the selected student will participate in the development of a highly versatile research tool that consists in the reconstitution of the eukaryotic actin-based machinery confined inside cell-sized lipidic vesicles, which mimic metastatic cells during their hematogenous dissemination. He will further use a recently developed method for the high-throughput mechanical analysis of free-floating particles and study the effect of the membrane and microenvironmental properties on the mechanical features of the resulting actomyosin cortex. Immunofluorescence and real-time imaging will be further used to characterize the actin networks.
Figure: Generation of actin networks (A) and cell-sized vesicles enclosing fluorescent proteins (B). Scale bars represents 2.5 μm in A and 5 μm in B.
Study the impact of the membrane composition and redox potential of the microenvironment on the formation and operation of the actomyosin cortex
Study the impact of the membrane composition and redox potential of the microenvironment on the formation and operation of the actomyosin cortex
Unai Silvan PhD E-mail: unai.silvan@hest.ethz.ch Institute for Biomechanics, ETH Zürich, Professorship Jess Snedeker
Unai Silvan PhD E-mail: unai.silvan@hest.ethz.ch Institute for Biomechanics, ETH Zürich, Professorship Jess Snedeker