Cells in our bodies constantly experience mechanical forces, whether externally applied or self-generated. The ability to respond to these forces is crucial for a variety of biological processes.
However, the mechanisms through which cells process mechanical stimuli are not well understood due to the absence of techniques to study these fine mechanical signals. Researchers at the University of Münster in Germany have developed a method to alter the mechanics of individual molecules and investigate their function within cells. Their findings have been published in the journal Science Advances.
Led by cell biologist Prof. Carsten Grashoff, the team developed a technique in which proteins can be modified using a light-sensitive molecule and controlled by short light pulses. This allowed them to break down individual proteins with precise temporal and spatial control, enabling the investigation of their mechanical importance in cells.
In their initial experiments, the researchers focused on two molecules that play a central role in cell adhesion and are implicated in various diseases. The talin protein is essential for carrying mechanical forces during cell adhesion in connective tissue, a critical process for cell migration. On the other hand, the desmoplakin protein is involved in resisting mechanical stress in cell-cell junctions found in epithelial tissues like the skin.
Mechanical stimuli, like other signals, are ultimately processed at the level of individual proteins within cells. While researchers have identified several molecules directly exposed to mechanical forces in cells in recent years, the mechanical contributions of individual proteins in complex cell-biological processes have often remained unclear.
Grashoff’s team utilized a light-sensitive connection that can withstand high levels of mechanical forces but breaks under light radiation. Similar light-sensitive proteins are found in plants, where they regulate the plant’s response to light. By introducing these predetermined breaking points into specific genes (talin, desmoplakin) using molecular biology techniques, the team created connective tissue and skin cells that could be controlled with laser beams at the protein level. The living cells, derived from mouse cell culture models, were then modulated and analyzed using fluorescence microscopy methods.
“These results provide evidence on how individual proteins can control the mechanical properties of specific cell structures,” says Grashoff.
As the technique is genetically encoded and can be inserted into the genome, the researchers anticipate its broad applicability in studying the mechanobiological properties of many other proteins in living cells, model organisms, and disease models.
More information:
Tanmay Sadhanasatish et al, A molecular optomechanics approach reveals functional relevance of force transduction across talin and desmoplakin, Science Advances (2023). DOI: 10.1126/sciadv.adg3347
Citation:
“Demonstrating the significance of individual molecules during mechanical stress in cells” (2023, June 21)
retrieved 22 June 2023
from https://phys.org/news/2023-06-significance-individual-molecules-mechanical-stress.html
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