Platelet-like Synthetic Cells with Shape Change, Triggered Secretion and Functional Adhesion

This project develops synthetic cells that mimic the essential functions of biological platelets – shape transformation, biochemical secretion, and mechanical adhesion – to promote blood clotting in a programmable and externally controllable manner. Platelets are among the simplest cells in the human body, yet they perform a complex and highly coordinated sequence of actions in response to vascular injury. The proposed synthetic cells emulate these sophisticated behaviors using light-activated control systems and biochemical recognition, enabling them to work in concert with natural platelets to initiate and reinforce clot formation. This work addresses a critical biomedical need by offering a potential solution to the persistent shortage of donor platelets used in trauma care, surgery, and cancer treatment. More broadly, the project demonstrates how synthetic cells can be engineered to interact functionally with living systems. The investigators are also implementing a robust educational outreach program that engages undergraduates, graduate students, K–12 teachers and students in hands-on research and classroom-based learning. By integrating cutting-edge research with multi-level education and outreach, this project trains the next generation of scientists and engineers. Synthetic cell research has made tremendous progress over several decades but now sits at a crossroads, where integrating multiple functionalities into a single synthetic cell remains elusive. This project aims to construct platelet-like synthetic cells with three coordinated, externally controllable capabilities. First, the project is developing light-responsive protein condensates that drive actin polymerization and cytoskeletal remodeling, enabling synthetic cells to undergo shape transformations that mimic platelet activation. Second, the team is engineering connexin nanopores that can be gated by near-infrared light to release dense granule components into the extracellular environment, thereby activating nearby natural platelets. Third, the project chemically reconstructs integrin complexes across synthetic cell membranes, forming transmembrane mechanical linkages that connect extracellular fibrin binding to intracellular actin networks. These three modules are developed independently and then integrated into a single synthetic cell platform capable of responding to external stimuli with precise spatiotemporal control. The resulting synthetic cells are evaluated in vitro for their ability to promote clot formation and activate natural platelets under both static and flow conditions. This project significantly advances the state of the art in synthetic cell engineering by demonstrating the coordinated function of multiple synthetic subsystems within a membrane-encapsulated platform. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.