Adherens junctions, the structures that allow cohesion between cells in a tissue, appear to be modulated by endothelial cell-to-cell tugging forces. Both the size of junctions and the magnitude of tugging force between cells grow or decay in concert with activation or inhibition of the molecular motor protein myosin.
The findings extend the understanding of multi-cellular mechanics. The dynamic adaptation of cell–cell adhesions to forces may explain how cells can maintain multi-cellular integrity in the face of different mechanical environments. Understanding how forces affect cell-cell adhesion could provide new opportunities for therapies targeting acute and chronic dysfunction of blood vessels.
Because these adhesions between endothelial cells are what allow these cells to form a tight seal between the blood inside vessels and the surrounding tissues, the research also suggests that changes in mechanical forces might induce endothelial cells to modulate the "tightness" of adhesions with each other, which may then modify the permeability of blood vessels. In many disease states, such as septic shock, diabetes and in tumor vasculature, endothelial cells fail to form the type of tight adhesions with each other that are necessary to prevent the vessels from leaking into the surrounding tissue.
It is known that myosin activity is required for cell-generated contractile forces and that myosin affects cellular organization within tissues through the generation of mechanical forces against the actin cytoskeleton; however, whether forces drive changes in the size of cell–cell adhesions remained an open question. The team demonstrated that, when “exercised,” the actomyosin cytoskeleton in a pair of cells can generate substantial tugging force on adherens junctions, and, in response, the junctions grow stronger. To prove a causal relationship, the group showed that exogenous forces, applied through a micromanipulator, also cause junction growth. This study marks the first time cell-generated forces at the adherens junction have been measured.
To investigate the responsiveness of adherens junctions to tugging force, bioengineer Chris Chen and his laboratory adapted a system of microfabricated force sensors to determine quantitative measurements of force and junction size. Researchers fabricated microneedles (3 microns wide, 9 microns tall, or one-fiftieth the size of a human hair) from a rubber polymer, polydimethylsiloxane, and coated them with an adhesive protein to allow cell attachment. This adhesive protein was transferred to the microneedle substrates in “bowtie patterns” which coaxed the cells to form pairs of cells with a single, cell-cell contact between them. Each cell in the pair attached to about 30 microneedles, and the researchers were able to measure the deflection of the needles as cells exerted traction (inward pulling) forces. The deflection of the needles was proportional to the amount of force generated by the structure.
“The role that physical forces play in cellular behavior has become better understood over the last ten years,” said Chen, the Skirkanich Professor of Innovation in bioengineering in the School of Engineering and Applied Science at Penn. “Now we know that cell structures under mechanical stress don’t necessarily break; they reinforce. Unlike passive adhesion such as with glue or tape, the cell-matrix and cell-cell adhesions that cells use as footholds to attach to surfaces and each-other are adaptive; when they experience force, they hold on tighter.”
In prior research, Chen’s team has demonstrated that the push and pull of cellular forces drives the buckling, extension and contraction of cells during tissue development. These processes ultimately shape the architecture of tissues and play an important role in coordinating cell signaling, gene expression and behavior, and they are essential for wound healing and tissue homeostasis in adult organisms.
This study was conducted by Chen, Zhijun Liu, Daniel M. Cohen, Michael T. Yang, Nathan J. Sniadecki and Sami Alom Ruiz of the Department of Bioengineering at Penn and John L. Tan and Celeste M. Nelson of the Johns Hopkins School of Medicine.
The research, published in the current issue of the journal Proceedings of the National Academy of Sciences, was funded by grants from the National Institutes of Health, Material Research Science and Engineering Center, Center for Engineering Cells and Regeneration of the University of Pennsylvania and Whitaker Foundation.
Jordan Reese | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy