During physiological processes, fibronectin fibers are believed to experience mechanical forces that strain the fibers and cause dramatic structural modifications that change their biological activity. While understanding the role of fibronectin strain events in development and disease progression is becoming increasingly important, detecting and interrogating these events is difficult.
In a new study, researchers identified molecular probes capable of selectively attaching to fibronectin fibers under different strain states, enabling the detection and examination of fibronectin strain events in both culture and living tissues.
"The mechano-sensitive molecular probes we identified allow us to dynamically examine the relevance of mechanical strain events within the natural cellular microenvironment and correlate these events with specific alterations in fibronectin associated with the progression of disease," said Thomas Barker, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
The study was published on April 23, 2012 in the online early edition of the journal Proceedings of the National Academy of Sciences. Barker worked on the study with Georgia Tech graduate student Lizhi Cao and Harry Bermudez, an assistant professor in the University of Massachusetts Amherst Department of Polymer Science and Engineering. The research was supported by the National Institutes of Health.
Researchers have hypothesized that mechanical forces emanating from cells may partially unfold fibronectin and regulate what proteins bind to it. While simulation and tissue culture experiments support this hypothesis, direct evidence that such molecular events occur in living organisms has not yet been presented, according to Barker.
A technique called intramolecular fluorescence resonance energy transfer (FRET) has been used to detect molecular strain events in fibronectin fibers, but the technique has limitations because it cannot be used on living tissues and requires the fibronectin to be chemically labeled.
"The molecular probes we identified can be used to map molecular strain events in native extracellular matrix and living lung tissues," explained Barker. "The probes can also be used to study the mechanism by which cells control the mechanical forces that alter fibronectin's conformation, control the exposure of its binding sites and regulate cell signaling."
The researchers used a controlled fibronectin fiber deposition and extension technique to apply tension to the fibers and stretch them to 2.6 times their original length without significant breakage. Then they used a technique called phage display to identify peptides capable of discriminating fibronectin fibers under relaxed and strained conditions. The molecular probes displaying peptide sequences LNLPHG and RFSAFY showed the greatest binding affinity to fibronectin fibers and the greatest efficiency in discriminating between relaxed and strained fibers.
For proof-of-concept demonstrations, the researchers used the probes to discriminate fibronectin fibers within native extracellular matrix and mouse lung slices. LNLPHG preferentially attached to relaxed fibronectin fibers, whereas RFSAFY bound to strained fibers. The probes never attached to the same fiber, which confirmed their ability to selectively discriminate regions within a fibronectin fiber network.
"This study strongly suggests that fibronectin fibers under strain display markedly different biochemical signatures that can be used for the molecular-level detection of fibronectin fiber strain," explained Barker. "The data also show the potential for living tissue to be interrogated for mechano-chemical alterations that lead to physiological and pathological progression."
In the future, the researchers hope to use these fibronectin strain-sensitive probes to target therapeutics to fibronectin fibers based on their mechanical signature.
This work was supported in part by training grants from the National Institutes of Health (NIH) (Award Nos. T32-GM008433 and T32-EB006343). The content is solely the responsibility of the principal investigators and does not necessarily represent the official views of the NIH.
Abby Robinson | EurekAlert!
Further reports about: > Barker > FRET > Ferchau Engineering > Molecular Target > RFSAFY > biological activity > extracellular matrix > fibronectin > fibronectin fibers > fibronectin strain > health services > intramolecular fluorescence resonance energy transfer > living organism > lung tissue > mechano-sensitive molecular probes > molecular probe > pathological progression > physiological process
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy