What causes one cell to stay "close to home", and another cell to detach and wander? How did they "sense" their physical environment and react to it? These questions touch the essence of every living cell, but the answers to them are not simple. In fact, the processes of sensing the environment and sticking to the substrate are performed by one molecular system, which is one of the most complex found in the living cell.
What causes one cell to stay "close to home", and another cell to detach and wander? How did they "sense" their physical environment and react to it? These questions touch the essence of every living cell, but the answers to them are not simple. In fact, the processes of sensing the environment and sticking to the substrate are performed by one molecular system, which is one of the most complex found in the living cell.
"Add to that the complexity of the cell's dynamic environment, and you get a complex that is difficult to define or describe in clear and precise terms," says Prof. Benjamin Giger from the department of molecular biology of the cell at the Weizmann Institute of Science.
Prof. Giger, together with Prof. Joachim Schaetz from the Max Planck Institute for Intelligent Systems in Stuttgart, Germany, recently inaugurated a project that presents a new approach to understanding the various ways in which cells adhere to their environment. The artificial system they created includes synthetic "cells" - which are actually vesicles made of a fatty membrane and a number of selected proteins - which "settle" on synthetic substrates with a defined and known structure. Through experiments with this simple model, which allows scientists to control every component of the system, they hope to derive new insights into the activity of the living cell. According to the two scientists, this is an ambitious plan, the contribution of which may be great: adhesion and sensing are essential activities for every biological process, starting with growth and development, ending with cell migration and tissue creation. When they go wrong, these physiological processes are affected, and cell changes occur, including, for example, the formation of cancer metastases.
The innovative research project is included in the field of science called synthetic biology: the adoption of nanoengineering approaches to study the cell and control its operations. Prof. Shapatz is a materials researcher, and Prof. Giger is a biologist. In recent years, the two have been working together to create unique synthetic substrates, which they use to test the sensing capabilities of living cells. Creating synthetic cells is the next and required step of this research.
The method for creating artificial cells begins with platelets - cell fragments capable of sticking to biological and artificial surfaces. The researchers isolate from the platelets the proteins that perform the adhesion, called integrins, and insert them into synthetic vesicles. At this stage, it is possible to add additional components of the infection system one by one, thus investigating each of them separately. At the same time, they plan to perform experiments on the surface to which the cells adhere through precise control of the properties of the surface itself, to the point of controlling the exact location of individual molecules. After analyzing the results obtained in the artificial system, the scientists will repeat the experiments with living cells, using the knowledge gained, to check how their synthetic model reflects reality - which is much more complex.
Even the seemingly simple synthetic models used by scientists are, in fact, very complex. "If we manage to identify the right combination of molecules that drives the cells to respond to the environment, we will define it as a great success," says Prof. Shapatz. In the continuation of the research, they plan to take another step beyond the current knowledge, which is based on an examination of a "grocery list" of hundreds of molecules that participate in the dialogue underlying the cell's infection and sensing mechanisms. This, in order to understand the way in which the individual components connect to a complete and active system.
The new research project has already registered significant success: it recently received a grant in the amount of three and a half million euros from the European Research Council (ERC). The European Council's grants are intended to "support significant advances on the front of knowledge, and encourage innovative and productive research, while applying unconventional approaches, and research at the interfaces between established scientific fields."