Artificial cells (ACs) aim to mimic certain features of the eukaryotic cell with the purpose ranging from studying the origin of life to developing AC-based therapeutics to support cells and tissues with compromised functions. There is a plethora of functional and structural features of the mammalian cell to be mimicked in the construction of an AC. Among those, energy generation is an important challenge to be addressed when self-sustained systems are desired as it is necessary to facilitate thermodynamically unfavorable processes. One approach to implement cellular functions in ACs is to use native organelles purified from mammalian donor cells. Here, mitochondria were isolated from hepatocytes to be employed as natural subunits that allow for chemically driven adenosine triphosphate (ATP) synthesis (<b>Figure 1</b>). The preserved inner membrane potential and respiration as well as the ATP production ability were confirmed in the isolated mitochondria. Viable mitochondria were further encapsulated in a gelatin-based hydrogel to evaluate their activity in a relevant AC carrier environment. Compared to mitochondria in solution, similar initial ATP production was observed and ATP production was sustained over 24 h in the hydrogel. Further, mitochondria were co-encapsulated with luciferase-loaded liposomes to facilitate the catalytic conversion of D-luciferin with mitochondrially produced ATP. Taken together, this effort demonstrates the potential of using mitochondria as an energy-generating module in ACs, which opens up new opportunities towards the facilitation of energy dependent processes and a broadening of enzymatic reactions to be implemented in ACs.

Mitochondria as ATP producing subunits in hydrogels towards energy generating artificial cells

ACS Spring Meeting 2021

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