Dresden, December 30
R esearchers from the University of California, Santa Barbara and the Cluster of Excellence Physics of Life at the Technical University of Dresden have discovered how cells sense their mechanical surroundings as they develop tissues during embryogenesis.
One of the most difficult and crucial jobs that cells must complete throughout embryogenesis is the development of tissues and organs. Cells communicate with one another during this cooperative endeavour through a range of communication techniques, such as biochemical signals (which are akin to a cell's sense of smell) and mechanical cues (which are similar to a cell's feeling of touch).
Cell communication has long captivated scientists across a multitude of fields. How cells use their sense of touch to make critical decisions during embryogenesis is still a mystery, but Professor Otger Campas and his team at the Physics of Life (PoL) Cluster of Excellence at Technische Universitat Dresden and the University of California Santa Barbara (UCSB) have now been able to solve it. Their article has since appeared in Nature Materials.
Testing the surroundings In their paper, the researchers report how cells within a living embryo mechanically test their environment and what mechanical parameters and structures they perceive. "We know much about how cells sense and respond to mechanical cues in a dish. However, their microenvironment is quite different within an embryo and we did not know what mechanical cues they perceive in living tissue," said Campas, Chair of Tissue Dynamics and PoL Managing Director.
The mechanical cures help cells make important decisions, such as whether or not to divide, move or even differentiate, the differentiation process by which stem cells turn into more specialized cells able to perform specific functions. Previous works revealed that stem cells on a synthetic substrate rely heavily on mechanical cues to make decisions Cells on surfaces with a stiffness similar to bones became osteoblasts (bone cells), whereas cells on surfaces with a stiffness similar to brain tissue became neurons. The findings greatly advanced the field of tissue engineering as researchers used these mechanical cues to create synthetic scaffolds to coax stem cells to develop into desired outcomes. These scaffolds are used today in a variety of biomedical applications.
From a dish to the living embryo However, a dish is not the cell's natural habitat. While building an organism, cells are not in contact with synthetic scaffolds in a flat dish, but rather with complex living materials in three dimensions.
Over the last decade, Prof. Campas' research group uncovered the mechanical cues that guide cells in the complex tissues of an embryo. Using a unique technique developed in his lab, the researchers could probe the living tissue in a similar way as cells do and find out what mechanical structures the cells sense. "We first studied how cells mechanically test their micro-environment as they differentiate and build the body axis of a vertebrate, as they differentiate," Campas said. "Cells used different protrusions to push and pull on their environment. So we quantified how fast and strong they were pushing." Using a ferromagnetic oil droplet that they inserted between developing cells and subjecting it to a controlled magnetic field, they were able to mimic these tiny forces and measure the mechanical response of the cell's surroundings.
Sensing the tissue architecture and cells change fate Critical to these embryonic cells' actions is their collective physical state, which Campas and his research group described in a previous paper to be that of an active foam, similar in consistency to soap suds or beer froth, with cells clumped together by cell adhesion and tugging of each other. What the cells are mechanically probing, Campas and team found out, is the collective state of this "living foam" -- how stiff it is and how confined the assemblage is. "And right at the moment that cells differentiate and decide to change their fate, there is a change in the material properties of the tissue that they perceive." According to him, the moment the cells within the tissue decide on their fate, the tissue falls its stiffness.
Researchers reveal how cells sense their mechanical environment
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