Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

May the cellular force be with you

10.12.2013
UC Santa Barbara assistant professor Otger Campas is one of the minds behind a new method for measuring the cellular forces that shape tissues and organs

Like tiny construction workers, cells sculpt embryonic tissues and organs in 3D space. This task is complicated and requires constant communication between cells to coordinate their actions and generate the forces that will shape their environment into complex tissue morphologies.


This is an image of cells in a mouse mandible (red and green) squeezing an oil droplet (cyan). The deformation of the droplet allows scientists to obtain the squeezing forces generated by the cells around the droplet.

Credit: Figure by Otger Campas

Biologists have long studied the communication between cells and their behavior while building these structures, but until now, it had not been possible to see the forces cells generate to shape them. A new method to quantify the mechanical forces that cells exert while building tissues and organs can help answer long unresolved questions in biology and provide new diagnostic tools for medicine.

Developed initially in the Wyss Institute at Harvard University by Otger Campàs and Donald Ingber, this technique is the first of its kind to measure the mechanical forces that cells generate in living embryos. Now an assistant professor who holds the Mellichamp Chair in Systems Biology at UC Santa Barbara, Campàs leads a lab that is developing this droplet technique in several new directions, and applying it to discover the patterns of cellular forces that shape embryonic structures in fish and chicken.

"There is a lot of interest in understanding how genetics and mechanics interplay to shape embryonic tissues," said Campàs. "I believe this technique will help many scientists explore the role that mechanical forces play in morphogenesis and, more generally, in biology."

So far, the vast majority of knowledge on how cellular forces affect cell behavior has come from cells studied in vitro — through cultures that isolate cells from their natural environment. Using soft gel substrates or gel matrices, researchers have been able to measure the traction forces of these cells moving in a petri dish. However, almost nothing is known about the forces that cells generate while sculpting embryonic tissues and organs, and how these affect cell behavior in their natural environment.

"In general, cells behave in a different way inside an embryo than in a dish," Campàs said. Some behaviors may be similar, but many others are not. Depending on the environment, cells respond in a variety of ways, he added.

"It has not been possible to demonstrate a direct causal relationship between mechanics and behavior in vivo because we previously had no way to directly quantify force levels at specific locations in 3D living tissues," said Donald Ingber, director of the Wyss Institute for Biologically Inspired Engineering at Harvard. "This method now allows us to make these measurements, and I hope it will bring mechanobiology to a new level."

To measure these miniscule forces, Campàs and Ingber, used tiny droplets of a special, flour-based oil. Once stabilized and with controlled surface tension, the droplet's surface chemistry is modified to allow for the adhesion of living cells. It is also fluorescently labeled to allow observers to see its shape. When cells push and pull on an oil droplet, they deform it, and this deformation provides a direct read-out of the forces they exert.

Using this technique, Campàs and Ingber showed that it is possible to measure cellular forces in different conditions, such as 3D cellular aggregates or in living mouse mandibles. Research findings for this work are published in the advance online version of the journal Nature Methods.

This method can help answer questions that biologists have been trying to answer for decades: What are the forces that cells generate to sculpt embryonic tissues and organs? And how do these forces affect cell behavior and gene expression in the cell's natural environment, the living embryo?

"Understanding how cells shape embryonic structures requires measuring the patterns of cellular forces while the structure is being built," said Campàs. "If you take the cells out of the embryo and put them in a dish, you don't have the tissue or organ structure anymore."

The knowledge gained by the ability to observe the behavior of developing cells as they mature could lead to further knowledge regarding a wide variety of conditions including birth defects or tumor growth and metastasis. Moreover, this method can also provide insight into diseases in which imbalances in forces exerted by tissues' constituent cells are an issue, according to Ingber.

"Examples include hyper contractility in airway smooth muscle cells in asthma; vascular smooth muscle cells in hypertension; intestinal smooth muscle in irritable bowel disease; skin connective tissue cells in contractures and scars, etc. as well as low contractility in heart muscle cells in heart failure, and so on," said Ingber. Investigating the forces behind tissue stiffness and contractility may also aid the diagnosis of tissue abnormalities.

In addition to Campàs and Ingber, the research team included L. Mahadevan, Wyss core faculty member and Lola England de Valpine, professor of applied mathematics at Harvard SEAS; David A. Weitz, Wyss associate faculty member and Mallinckrodt Professor of Physics and Applied Physics at Harvard SEAS; Tadanori Mammoto, instructor at Harvard Medical school and Boston Children's Hospital; Sean Hasso, a former postdoctoral reseracher at Boston Children's Hospital; Ralph A. Sperling, a former postdoctoral researcher at Harvard SEAS; Daniel O'Connell, a former graduate student at Harvard Medical School; Ashley Bischof, a former graduate student at Boston Children's Hospital; Richard Maas, M.D., a professor of genetics at Harvard Medical School. The work was funded by the National Institutes of Health SysCode Consortium, the MacArthur Foundation, the Harvard NSF-MRSEC and the Wyss Institute.

Sonia Fernandez | EurekAlert!
Further information:
http://www.ucsb.edu

More articles from Life Sciences:

nachricht If Machines Could Smell ...
19.07.2019 | Fraunhofer-Institut für Produktionstechnik und Automatisierung IPA

nachricht Algae-killing viruses spur nutrient recycling in oceans
18.07.2019 | Rutgers University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Better thermal conductivity by adjusting the arrangement of atoms

Adjusting the thermal conductivity of materials is one of the challenges nanoscience is currently facing. Together with colleagues from the Netherlands and Spain, researchers from the University of Basel have shown that the atomic vibrations that determine heat generation in nanowires can be controlled through the arrangement of atoms alone. The scientists will publish the results shortly in the journal Nano Letters.

In the electronics and computer industry, components are becoming ever smaller and more powerful. However, there are problems with the heat generation. It is...

Im Focus: First-ever visualizations of electrical gating effects on electronic structure

Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.

Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

Im Focus: Extremely hard yet metallically conductive: Bayreuth researchers develop novel material with high-tech prospects

An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".

The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Heat flow through single molecules detected

19.07.2019 | Physics and Astronomy

Heat transport through single molecules

19.07.2019 | Physics and Astronomy

Welcome Committee for Comets

19.07.2019 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>