The primary aims of this work are tightly connected: (i) development of a bio-inspired “synthetic cell” capable of self-assembling, self-propelling and environmental sensing prepared with reduced molecular complexity compared to living cells (ii) quantitative assessment of the bio-activity of specific cellular components within these “synthetic cells”, leading to better fundamental understanding of their function in living cells (iii) use of these findings for reverse engineering of living cells with tailored adhesive and sensory properties.
Integrin based adhesion has been shown to participate in numerous processes in living cells, which sense, via their adhesions, multiple environmental cues, integrate them, and develop a complex, multi-parametric response. However, due to their intrinsic molecular complexity the specific functional roles of different components of the adhesion site are still poorly understood. To address this issue, we will utilize current knowledge of the modular nature of focal adhesions and related integrin-mediated extracellular matrix contacts to develop “synthetic cell” models, consisting of large lipid vesicles, functionalized by transmembrane integrins, various integrin-binding proteins and specific sets of scaffolding and signaling proteins of the adhesion sites. The one-by-one loading of these vesicles by micro-injection with these proteins will allow tight control of the system composition and complexity, and testing of the effect of compositional and environmental variations on the adhesion and signaling features. The “synthetic cells” will be plated on adhesive matrices displaying specific spatial, chemical and mechanical features for testing their chemical and mechanical sensing capabilities. The datasets produced in these experiments will provide a solid basis for reverse engineering perturbations of living cells, in which specific functional pathways will be targeted and/or modified to modulate living cells' functionality.
Field of science
- /natural sciences/biological sciences/synthetic biology
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins
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