According to Rudolf Virchow, the father of modern pathology, “Diseases arise from malfunctioning cells.” Since its inception in the 1800s, this theory which forms the basis of cellular pathology has influenced how scientists view disease and the approach used in the development of effective therapy for diseases. These therapies target malfunctioning cells; However, the scientific community continues to seek ways to build cells that may one day replace malfunctioning cells, thus ushering the world into a new age of effective patient care and treatment. The development of microcapsules (later known as artificial cells) by Thomas Chang started this era of synthetic cell development and in 2010, the first-ever synthetic cell with a synthetic genome was created. However, none of these artificial cells contained structures that mimicked the normal cell cytoskeleton. This is why the cell developed by Scientists from the 2nd Physics Institute at the University of Stuttgart and colleagues from the Max Planck Institute for Medical Research represents a huge leap in the aspect of cell and genetic biology. Their research published in Nature Chemistry shows the result of incorporating functional DNA-based cytoskeleton into synthetic cell compartments and its relevance in clinical practice.
Mimicking the cell cytoskeleton
The cytoskeleton plays a very crucial role in numerous cellular functions. Aside from the basic function of giving the cell its shape, it is important for cell division, intracellular transport, movement in response to stimuli, and the determination of cellular polarity. To effectively mimic this cellular structure, the team took into consideration certain key features of this framework, such as its stability, quick adaptability, and reactivity to triggers, when developing the synthetic cytoskeleton.
Applying the principle of DNA nanotechnology, they developed DNA-based variants of the meshwork. They assembled DNA into micron-scaled filaments, which constituted the basis of the synthetic cytoskeleton. The filaments were then equipped with diverse functions characteristic of the cellular cytoskeleton, such as assembly and disassembly upon stimulation.
The team successfully induced vesicular transport along the filaments of the synthesized cytoskeleton. The result showed that this transport accurately mimicked the burnt-bridge vesicular transport mechanism observed in cells.
This study was not without problems. However, the most daunting of the challenges faced was the slow transport speed observed in the developed cytoskeletal structure. This slow transport was attributed to the inability of the team to fine-tune the energy landscapes involved in the DNA-based cytoskeleton’s assembly and disassembly.
Current therapy for the treatment of diseases focuses on malfunctioning cells. Drugs that target these cells to correct errors in cellular development have been developed: however, like stem cell transplants, synthetic cells could be used to replace non-functioning cells. Additionally, these cells could be used for on-site production of various compounds necessary for health, such as insulin, and other proteins whose deficiency has resulted in diseases that currently plague mankind. This study brings us one step closer to achieving this goal.
Before now, DNA nanotechnology has been used in the development of other cellular components like ion channels and or cell-cell linkers. This study, which is the first of its kind to apply this principle in developing the cell cytoskeleton, represents a groundbreaking step toward the synthesis of cells that may one day replace malfunctioning human cells and change our view of the cell.