Artificial cells with communicative features, toward hybrid organoids


Van Hest, Jan (Eindhoven University of Technology)


Artificial cells have been topic of intensive investigation over the past years. Although in first instance they have been mainly developed as a platform to attain a better fundamental understanding how living cells operate, they have recently also been recognized as interesting structures in biomedical research. In this lecture I will discuss an artificial cell system based on complex coacervates as developed in our group. These are formed by the mixing of two oppositely charged amylose derivatives that spontaneously interact and phase separate into a polymer-rich and polymer-depleted water phase. The coacervate microdroplets that are in first instance created are prevented from coalescence and further growth by a stabilizing polymer membrane. Coacervates droplets are interesting cell mimics since their crowdedness shows similarities to the dense cytoplasm of living cells. Furthermore, they have the ability to effectively sequester cargo. The polymer membrane we have created not only provides stabilization, but also allows exchange of molecules with the outside environment. We have demonstrated that biocatalytic cascades can be efficiently executed within one artificial cell, as a result of the high accumulation (150 fold) of the enzymes in the coacervate core. Furthermore, we have also been able to achieve uptake of protein cargo using affinity tagging; by incorporation of a Ni-NTA moiety in the coacervate, His-tagged protein were taken up highly effectively. By enzymatic removal of the His tag the proteins could also be controllably released. We have extended this uptake and release behavior to a DNA mechanism, which now allows for reversible shuttling of proteins in and out of the artificial cell, and between artificial cells. We have also investigated the biocompatibility of our artificial cells when in contact with living cells. After appropriate purification procedures we could demonstrate that the artificial cells are well tolerated. These developments have now opened up the way to combine artificial cells with living cells in the formation of organoids, in which the artificial cells are used as sending units of growth factors with spatiotemporal control.


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