ConspectusCells are highly advanced microreactors that form the basis of
all life. Their fascinating complexity has inspired scientists to
create analogs from synthetic and natural components using a bottom-up
approach. The ultimate goal here is to assemble a fully man-made cell
that displays functionality and adaptivity as advanced as that found
in nature, which will not only provide insight into the fundamental
processes in natural cells but also pave the way for new applications
of such artificial cells.In this Account, we highlight our
recent work and that of others
on the construction of artificial cells. First, we will introduce
the key features that characterize a living system; next, we will
discuss how these have been imitated in artificial cells. First, compartmentalization
is crucial to separate the inner chemical milieu from the external
environment. Current state-of-the-art artificial cells comprise subcompartments
to mimic the hierarchical architecture of eukaryotic cells and tissue.
Furthermore, synthetic gene circuits have been used to encode genetic
information that creates complex behavior like pulses or feedback.
Additionally, artificial cells have to reproduce to maintain a population.
Controlled growth and fission of synthetic compartments have been
demonstrated, but the extensive regulation of cell division in nature
is still unmatched.Here, we also point out important challenges
the field needs to
overcome to realize its full potential. As artificial cells integrate
increasing orders of functionality, maintaining a supporting metabolism
that can regenerate key metabolites becomes crucial. Furthermore,
life does not operate in isolation. Natural cells constantly sense
their environment, exchange (chemical) signals, and can move toward
a chemoattractant. Here, we specifically explore recent efforts to
reproduce such adaptivity in artificial cells. For instance, synthetic
compartments have been produced that can recruit proteins to the membrane
upon an external stimulus or modulate their membrane composition and
permeability to control their interaction with the environment. A
next step would be the communication of artificial cells with either
bacteria or another artificial cell. Indeed, examples of such primitive
chemical signaling are presented. Finally, motility is important for
many organisms and has, therefore, also been pursued in synthetic
systems. Synthetic compartments that were designed to move in a directed,
controlled manner have been assembled, and directed movement toward
a chemical attractant is among one of the most life-like directions
currently under research.Although the bottom-up construction
of an artificial cell that
can be truly considered “alive” is still an ambitious
goal, the recent work discussed in this Account shows that this is
an active field with contributions from diverse disciplines like materials
chemistry and biochemistry. Notably, research during the past decade
has already provided valuable insights into complex synthetic systems
with life-like properties...