enCAPS · Engineering Synthetic Cells for Artificial Phagocytosis with Superselectivity

enCAPS will produce the first Phagocytic Synthetic Cell capable of superselective artificial phagocytosis. Artificial phagocytosis aims to mimic the complex mechanisms used by cells to internalize materials in minimal engineered systems, achieving a major milestone in the construction of advanced synthetic cells. This endeavour faces two main challenges: the energy barriers to particle internalization upon membrane bending, and the lack of selectivity. Previous approaches using liposomes or polymersomes did not sufficiently address these two challenges, since liposomes lack stability and polymersomes have rigid membranes. To go beyond the state-of-the-art, I will use a new class of membrane-forming polymers: ionically linked comb polymers. They self-assemble in i-combisomes with high stability and flexibility, providing an ideal platform for phagocytic synthetic cells. By carefully designing the molecular structure and the statistic composition of the polymers, I will dissect how structural variations in the molecular composition can serve to store potential energy that can be released to facilitate the engulfment. Subsequently, I will seek to introduce principles of superselectivity to particle interactions with i-combisomes, achieving an ON/OFF type response. Here I will unveil the interplay of binding strength, receptors mobility, and clustering on the membrane using supported bilayers. This will be translated to free-standing i-combisomes, generating a superselective synthetic cell that can bind and internalize particles with specific surface decorations. To demonstrate the flexibility of this approach, several colloidal systems will be internalized. Thus, enCAPS will yield general design principles for superselective artificial phagocytosis. Due to its deep interdisciplinary, enCAPS will impact several fields, providing the blueprint for new nanocarriers, theragnostic devices, and advanced synthetic cells.