Coacervate-Controlled Membrane Remodelling and Connecting of Synthetic Cells

Objetivo

Membranes are crucial for the functioning of living cells. They enclose and protect the cell and organize the cellular machinery in subcompartments. Membrane proteins regulate the transport of molecules entering and exiting the cell, which is essential for homeostasis and energy production. However, transmembrane transport, shape regulation and division also present major challenges for creating synthetic cells and integrating synthetic and living cells. Without complex transport proteins, vesicle-based synthetic cells cannot take up nutrients, excrete waste or stay alive. Moreover, connecting synthetic cells into functional synthetic tissues capable of communication has proven difficult. Emerging evidence shows that, in living cells, biomolecular condensates are involved in a wide range of functional interactions with cellular membranes, leading to signalling, membrane repair, remodelling and exocytosis.

This proposal aims to develop coacervate protocells with dynamically controlled properties that are capable of similar functional interactions in synthetic cells, and at the interface between synthetic and living cells. The coacervates proposed here have three vital functions: (1) supply nutrients and functional biomolecules via triggered delivery; (2) reshape and divide synthetic cells; and (3) connect cells into synthetic tissues with tunable communication and mechanical properties. Key to these coacervates is the ability to dynamically control their interaction with membranes, which we achieve via active (bio)chemical reactions that we develop. Controlling this unique coacervate-membrane interface will be a gamechanger for building viable synthetic cells and tissues, and synthetic/live cell hybrids by creating new opportunities for delivery, remodelling and signalling, and provide a fundamental understanding of condensate-membrane interactions in biology.