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Building tissues and organs is one of the
most complex and fundamental tasks that cells must complete during embryogenesis.
In this collective task, cells communicate through a variety of communication methods, including biochemical signals (similar to the cell's sense of smell) and mechanical signals (the cell's sense of touch).
Researchers in a variety of disciplines have been fascinated
by cellular communication for decades.
Professor Otger Campà and colleagues have now been able to solve another mystery surrounding how cells use their sense of touch to make important decisions during embryogenesis
.
Their paper has now been published in
the journal Nature Materials.
In their paper, the researchers report how cells in living embryos mechanically test their environment, as well as the mechanical parameters and structures
they perceive.
"We know a lot about
how cells sense and respond to mechanical cues in a dish.
However, their microenvironment is completely different in embryos, and we don't know what mechanical cues they perceive in living tissue," says
Campàs, chair of tissue dynamics and managing director of PoL.
Mechanical therapy helps cells make important decisions, such as whether to divide, move, or even differentiate, and stem cells become more specialized cells through the differentiation process, capable of performing specific functions
.
Previous studies have shown that stem cells placed on a synthetic matrix rely heavily on mechanical signals to make decisions: cells with a surface hardness similar to bone become osteoblasts (bone cells), while cells with a surface hardness similar to brain tissue become neurons
.
This discovery gave a huge boost to the field of tissue engineering, as researchers used these mechanical cues to create synthetic scaffolds to induce stem cells to develop into desired results
.
These scaffolds are used today in a variety of biomedical applications
.
From Petri dishes to live embryos
However, petri dishes are not a natural habitat
for cells.
In the process of building an organism, cells come into contact not with synthetic scaffolds in plates, but with complex living materials in three dimensions
.
Over the past decade, Professor Campàs' research group has discovered mechanistic clues
that guide cells in embryonic complex tissues.
Using a unique technique developed in his lab, researchers can probe living tissue in a cell-like manner and figure out the mechanical structures
that cells perceive.
"We first looked at how cells mechanically test their microenvironment when they differentiate and build vertebrate body axes
when they differentiate," Campàs said.
Cells use different protrusions to push and pull the environment
.
So we quantified the speed and intensity
of their push.
”
They inserted ferromagnetic oil droplets between developing cells and placed them in a controlled magnetic field, where they were able to simulate these tiny forces and measure the mechanical response
of the environment around the cell.
Sensing tissue structure and cells change fate
Critical to the behavior of these embryonic cells is their collective physical state, which Campàs and his team described in a previous paper as an active foam, similar to soap foam or beer foam, where cells clump together
through cell adhesion and pulling on each other.
Campàs and team found that the cell mechanically detected the collective state of this "living bubble"—how rigid it was and how limited
its combination was.
"At the moment when cells differentiate and decide to change their fate, the material properties of the tissues they perceive change
.
" According to him, the tissue loses its hardness
the moment the cells within the tissue decide their own fate.
Looking to the future
What has not been confirmed in this study is the complex question of whether changes in stiffness in the embryonic environment lead to changes in cell state and, if so, how
.
"There is an interaction between the mechanical features of structures that cells collectively construct, such as tissues or organs, and the decisions they make individually, because those decisions depend on the mechanical cues
that cells perceive in the tissue.
This interaction is central
to how nature constructs living things.
”
The findings of this study may also have important implications for
tissue engineering.
Potential materials that mimic the foam-like character of embryonic tissue, rather than widely used synthetic polymers or gel scaffolds, may allow researchers to create stronger and more complex synthetic tissues, organs, and implants in the lab, with the appropriate geometry and mechanical properties to achieve the desired function
.