The cells are so densely packed with proteins and other molecules that the situation is comparable to a subway ride in a big city after work. This so-called "crowding" sounds like a lot of stress, but it is essential for the biochemical processes in the cell—and, thus, for its health. In this way, proteins and molecules come into contact and can interact. Interactions such as hydrophobic and electrostatic interactions, as well as hydrogen bonds, can lead to various chemical reactions that are essential for the cell to survive. However, we hypothesize that interactions caused by crowding could also be harmful, potentially leading to diseases such as Alzheimer's or Huntington's disease. Both are well-known progressive neurological diseases that cannot be cured yet.
Although crowding is essential, it remains a question of how the biochemical equilibrium in cells is controlled. We aimed to map and understand these crowding effects with our project PArtCell (Physiologically Crowded Artificial Cells for Relevant Drug Screens). In addition, our goal was to develop physiologically relevant platforms that can be applied to screen new drugs for treating diseases such as Huntington's in these dense environments. We are developing approaches in natural and artificial cell systems that we aimed compare to each other to make the most relevant artificial cells possible. Compared to living cells, analyses of their synthetic counterparts have several advantages – for example, natural cells are influenced by many unknown parameters. In artificial cells, on the other hand, the initial conditions can be defined and thus controlled primarily.
We concluded with the ability to generate various relevant crowded artificial cells for studying protein aggregation and sensors to map their physiologically relevant environment, as well as validation against living cells. We further demonstrated methodology to observe aggregation in detail, displaying the impact of the environment on aggregate morphologies.
