Abstract
The bottom-up construction of synthetic cells from molecular components is arguably one of the most challenging areas of research in the life sciences. We review the impact of confining biological systems in synthetic vesicles. Complex cell-like systems require control of the internal pH, ionic strength, (macro)molecular crowding, redox state and metabolic energy conservation. These physicochemical parameters influence protein activity and need to be maintained within limits to ensure the system remains in steady-state. We present the physicochemical considerations for building synthetic cells with dimensions ranging from the smallest prokaryotes to eukaryotic cells.
Highlights
Cells are products of billions of years of evolution
Physicochemical conditions affect the activity of biological systems, both individually and synergistically
Physicochemical homeostasis is key for living and synthetic cells
Summary
Cells are products of billions of years of evolution. The molecular machinery of each cell is a complicated network, optimized for the particular set of conditions the organism faces. This makes diffusion slow over long distances (>10 s for 20 mm vesicle, see Figure 3B) [94] In these cases, filamentous structures or vesicular systems in which the internal medium is confined to regions near the membrane, like the cytoplasm in giant bacteria [86], would have an advantage over spherical vesicles, since the surface-to-volume ratio is higher. Stochastic effects are random events that depend on the size and the shape of the (vesicle) system, and on the concentration of its components, e.g. the enzymes enclosed in the vesicle lumen and the proteins embedded in the membrane In small volumes such as sub-micrometer vesicles, macromolecules will be present in low numbers due to their large size (Figure 3C), which results in higher stochasticity. We know that the conditions the early life forms experienced were most likely far more extreme in terms of temperature, pressure, radiation and concentration of ions than those of the majority of today’s cells [111]
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