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Instant insight: Making synthetic cells
05 October 2009
Cell and organelle mimics typically perform one simple function. Frank Caruso and team at the University of Melbourne, Australia, contemplate more complicated systems
Artificial cells and organelles are expected to become powerful therapeutic tools to perform missing or lost cell functions - essentially to make, convert or degrade biomolecules. Amongst their potential applications, replenishing absent or malfunctioning enzymes is a valuable goal as this might provide a long-term solution for chronic diseases. But the field is still in its infancy, with the most successful examples of synthetic cells and organelles typically performing only a single, simple function.
Synthetic mimics (left) can share many similarities with biological cells (right)
The field has also been boosted significantly by the advent of polymer capsules assembled by layer-by-layer techniques. In this procedure interacting polymers are deposited sequentially onto a sacrificial colloidal template which is eventually removed. Two prominent polymer pairs that form stable, micrometre- or smaller-sized capsules are based on poly(allylamine hydrochloride)/polystyrene sulfonate and poly(N-vinyl pyrrolidone)/poly(methacrylic acid). While the former capsules are not biodegradable and have potential use in creating organelles with extended lifetimes, the latter polymer pair is used to obtain biodegradable capsules stabilised by deconstructible disulfide linkages.
Progress in cargo loading has meant that peptides, nucleic acids and intact proteins can be trapped inside such polymer capsules, making them particularly promising candidates in the design of therapeutic artificial cells and organelles. The first examples of enzymatic reactions within the capsules have brought these vehicles one step closer towards this. The most well studied class of these reactions involves the enzyme-catalysed conversion of small molecules, as the capsules' semipermeable nature allows small substrates and products (for example ions) to diffuse in and out while the larger macromolecules are blocked.
A number of enzymes have now been successfully encapsulated, retained their activity and performed their function within capsules. We recently reported DNA degradation triggered by a nuclease within a polymer capsule, a function reminiscent of that of the cellular lysosome, an organelle containing several digestive enzymes. This was one of the first examples of a layer-by-layer assembled capsule mimicking an organelle.
A nature-inspired approach towards synthetic reactors that allow multiple, spatially separated and parallel reactions, requires that the vessels be subdivided. Specific examples include two-compartment polymer capsules, smaller lipid or polymeric vesicles embedded in larger vesicles, and smaller capsules embedded in cross-linked gel beads.
The progress in the design of layer-by-layer-derived polymer capsules, including the choice of building blocks to obtain stable capsules, the creation of subdivided systems, and the successful encapsulation of enzyme-catalysed reactions, illustrate the potential of these vehicles as synthetic cell and organelle mimics. While many challenges still need to be addressed, including creating systems that can self-replicate, self-repair, and recognise a target, the field is undoubtably on the verge of creating medically relevant examples.
Read more in the Minireview 'Polymer hydrogel capsules: en route toward synthetic cellular systems' in Nanoscale.
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Link to journal article
Polymer hydrogel capsules: en route toward synthetic cellular systems
Brigitte Städler, Andrew D. Price, Rona Chandrawati, Leticia Hosta-Rigau, Alexander N. Zelikin and Frank Caruso, Nanoscale, 2009, 1, 68
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