Bottom-up synthetic biology for building artificial platelets

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Allen Liu, Victoria Murray, Elisabeth Steel

University of Michigan, United States

The field of synthetic biology has recently emerged as a result of achieving a critical mass in our knowledge of biology. While many biological molecules and systems are still too complex to be rationally designed de novo, the continued efforts in isolation and characterization of individual biological components offer the possibility of integrating them into biologically inspired devices that exhibit novel functionalities. Rather than deconstructing existing biological systems, our vision is to assemble biological parts into systems. As a first step in this direction, we seek to emulate biological systems that would have immediate benefit and also serve as a test-bed for such design strategy. To this end, we have identified platelets as a tractable first target. Platelets are anucleate cells that are pre-programmed to execute a fixed pattern of behaviors that lead to the activation of the clotting cascade. Our synthetic biology approach requires more than reconstitution of the parts that make up a platelet. Rather, we propose designing an artificial platelet that is based on mimicking the functionality of a natural platelet, through a novel combination of biological components. Our approach includes incorporating mechanosensitive channels, phosphatidylserine scramblase, and phosphatylserine synthase into lipid vesicles that would activate the clotting cascade when bound to injured vasculature. A plan for building artificial platelets by breaking this challenging problem into manageable modules will be described and our progress in testing the design strategies will be reported.