Working in the labs of Whitehead Member Paul Matsudaira and MIT professor Douglas Lauffenburger, postdoctoral researcher Muhammad Zaman discovered that cells move quite differently in three dimensions. His study, which focused on human prostate tumor cells, appeared this week in the online early edition of Proceedings of the National Academy of Sciences.
"Two-dimensional assays ignore the obstacles that cells face in their natural contexts," explains Zaman, who recently became an assistant professor at the University of Texas at Austin. "In 3D, cells move through a thick jungle of fibers, or "vines"TM, that hinder forward progress."
Cells must either squeeze through or chop up these putative vines to get anywhere. As a result, they move slower in three dimensions.
In an interesting twist, all cells need at least some vines to move, as they latch onto the "branches" with claw-like proteins called integrins and pull themselves forward. When Zaman disabled some of these claws, in a manner analogous to certain anti-cancer drugs, the cells moving across the top of the jungle canopy (in two dimensions) needed a greater number of vines to keep up their pace, while cells plowing through the jungle instead needed vines chopped to maintain the same speed. The complexity of this situation is further increased in that the cells become dramatically sensitive to the stiffness of the vines when the integrins are disabled and consequently tend to squeeze through the vines rather than pushing them aside.
"Our findings help explain why two-dimensional assays for metastasis-inhibiting drugs do not effectively predict their effects in tissue," says Lauffenburger, who is director of MITâ€TMs Biological Engineering Division. He believes pharmaceutical companies will eventually use three-dimensional assays, accompanied by appropriate computational models such as that also recently published by Zaman (in Biophysical Journal in 2005), to determine how drugs affect metastasis.
But technology must improve before more complicated 3D studies are attempted. For his 3D work Zaman worked with one sample at a time, using a special confocal microscope at the Whitehead-MIT BioImaging Center. The microscope divided each specimen into virtual slices, generating a new stack of images every 15 minutes.
"It took me about a year to get enough data because the microscope wasnâ€TMt designed for high-throughput experiments," he says. Fortunately, the BioImaging Center has one of the most powerful sets of computers at MIT and the imaging processing and analysis went quite quickly.
"Muhammad was successful for two reasons," says Matsudaira. "His computational model predicted what would happen in virtual experiments and then he was able to go straight to test the predictions with these complicated 3D experiments. As a result, the sophisticated models of cell movement enhance our understanding of key biological processes, including metastasis."
David Cameron | EurekAlert!
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Health and Medicine
27.04.2017 | Information Technology
26.04.2017 | Materials Sciences