The cytoskeleton is a matrix of different structural proteins that is vital in the functioning of cells. It maintains the shape of the cells, anchors organelles in the right position, enables the movement of cell components, and aids cellular response to stimuli and biological processes. It is also involved in the cell signaling pathways.
synthetic cytoskeleton Credit: Nature Chemistry
Cytoskeleton has three types of structural components; microtubules, microfilaments, and intermediate filaments. The ability for it to transform from filament networks to aligned spindles is regulated by numerous proteins associated with it. These proteins are responsible for fiber elongation, cross-linking, and a host of other functions.
So many studies have looked into this mechanism of cytoskeletal functioning. Purified proteins have been rebuilt with vesicles which were used to analyze the effect of actin and other proteins like filamin or fascin on cell shape.
Peptides for artificial cytoskeleton
The bottom-up synthetic approach refers to the construction of a cell from scratch and applying this new cell to biological processes. Recently, scientists have built synthetic cytoskeletons from scratch and this has been seen as a new way to create artificial cells. They have achieved this by adding crowding agents or salt to cause bundling of DNA. Other methods are assembling cellular structures to the outside or inside of lipid droplets, and the use of peptides.
Peptides are not popularly used, however, they have shown promise as building blocks for the development of an artificial cytoskeleton. A lot of mechanisms involving peptides have been studied, however, only a few have been discovered in cell-like confinement. Scientists suggest that the use of peptides to produce artificial cytoskeleton is very useful.
Actin and DNA crosslinks
Margaret Daly et al conducted a study that integrated peptides and DNA cross-links for the production of artificial cytoskeleton in lipid droplets. The creation was done with actin-binding protein bundles leading to a Peptide-DNA crosslink with varying geometry and sequence. The study showed how the structures were localized in the lumen of the lipid droplets and how the different changes occurred.
They noticed that actin filaments and DNA crosslinks interact to form filopodia, mesoscale, and the cell cortex. They also noticed that fascin caused actin filaments to form bundles while filamin forms crosslinks with actin to create a network in the cell cortex.
Clinical significance
These results have established that a cytoskeleton can be created from scratch using actin bundles and DNA crosslinks in lipid droplets. Scientists propose that the shape of cells can further be fine-tuned by changing the lipid composition to alter the membrane properties of the DNA crosslinks.
The peptide-DNA crosslink design is a powerful strategy for the development of artificial cells from scratch. It can be applied to regenerative medicine, drug delivery systems, and diagnostic tools.
References
Daly, M.L., Nishi, K., Klawa, S.J. et al. Designer peptide–DNA cytoskeletons regulate the function of synthetic cells. Nat. Chem. (2024). https://doi.org/10.1038/s41557-024-01509-w
FEEDBACK:
