Molecular motors direct the fate of stem cells

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Scientists at the University of Groningen and the University Medical Center Groningen used molecular motors to manipulate the protein matrix on which bone marrow-derived mesenchymal stem cells are grown. Rotating motors altered the protein structure, which resulted in a bias of the stem cells to differentiate into bone cells (osteoblasts). Without rotation, the stem cells tended to remain multipotent. These results, which could be used in tissue engineering, were published in Science Advances on 29 January.

‘Cells are sensitive to the structure of the surface that they attach to,’ explains Patrick van Rijn, associate professor in Materiobiology and Nanobiomaterials. ‘And movement is an important driver in biology, especially continuous movement.’ That is why Van Rijn and Feringa and their colleagues decided to use molecular motors to manipulate the protein matrix on which stem cells are grown. The light-driven motor molecules were designed by the 2016 Nobel Laureate in Chemistry Ben Feringa.


Structural changes

The scientists linked molecular motors to a glass surface. Subsequently, the surface was coated with protein and either exposed to UV irradiation to power the motors or not exposed to it at all. After about an hour, the motor movement was stopped and cells were seeded onto the protein layer and left to attach. Finally, differentiation factors were added. These experiments showed that cells grown on protein that was submitted to the rotary motion of the molecular motors tended to specialize into bone cells more often, while cells seeded on protein that was not disturbed were more inclined to maintain their stem-cell properties.

Observations of the protein layer using atomic force microscopy and simulations of the interaction between the motor molecules and proteins, performed by Prof. Marrink’s research group, showed that the movement induced subtle structural changes in the protein matrix. ‘The movement of motor molecules interferes with the alpha-helices in the proteins, which causes structural changes,’ explains Van Rijn. He compares it to the difference in texture between an unwhipped egg white and a whipped one.

Cell fate

The change in the surface structure of the adhered protein affects how the cells attach, for example how much they stretch out. This sets off a signaling cascade that eventually leads to altered behavior, such as the differentiation into bone cells. Thus, molecular movement leads to nanoscopic changes in surface structure, which in turn leads to differences in cell attachment, cell morphology and eventually, cell differentiation. ‘It’s like a domino effect, where smaller stones consecutively topple slightly larger ones so that a large effect can be achieved with a small trigger.’

‘Changing the properties of a surface to affect cell fate has been used before,’ says Van Rijn. However, this was done primarily with switches, so there was just a change from one state to another. ‘In our study, we had continuous movement, which is much more in line with the continuous motion found in biological transport and communication systems. The fact that the motors are driven by light is important,’ Van Rijn adds. ‘Light can be carefully controlled in space and time. This would allow us to create complex geometries in the growth matrix, which then result in different properties for the cells.’ Therefore, light-controlled molecular motors could be a useful tool in tissue engineering.

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Extreme weather conditions can tax urban drainage systems to the max

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A recently published paper from the School of Engineering says existing design methods for urban drainage systems aren’t going far enough to withstand possible catastrophic storms or even unpredictable failures during a moderate storm.

“As engineers, we run simulations of possible catastrophic events, and current systems often do not fare well,” says doctoral student Saeed Mohammadiun. “We are seeing sources of overloading such as structural failures, severe rainfalls or abrupt snowmelt stressing these systems.”

Add any extreme situation including quick snowmelt or a heavy and sudden rainfall, and Mohammadiun says many systems aren’t built to handle these worst-case scenarios. Mohammadiun has conducted several case studies of drainage systems in major urban areas around the world. He has determined many current urban standards designed for a 10-to-50 or even 100-year storm scenario are not meeting the increasing demands of climate change as well as intrinsic failure risk of networks’ elements.


“Conventional, reliability-based design methods only provide acceptable performance under expected conditions of loading,” he says. “Depending on the system, if something breaks down or there is a blockage, it can result in a failure and possible flooding.”

According to Mohammadiun, the resiliency of a system is not just dependent on the load it can handle, but also on its design and build. Many do not take into account the effects of climate change or unexpected weather conditions.

To establish an efficient resilient system, Mohammadiun says it is important to consider various sources of uncertainty such as rainfall characteristics, heavy snowfalls followed by a quick melt and different possible malfunction scenarios along with budget constraints, he says.

“Building or improving the resilience of urban stormwater drainage systems is crucial to ensuring these systems are protected against failure as much as possible, or they can quickly recover from a potential failure,” he adds. “This resilient capacity will provide urban drainage systems with the desired adaptability to a wide range of unexpected failures during their service life.”

The research points to several measures municipalities can proactively address the issue. Municipalities could build bypass lines and apply an appropriate combination of relief tunnels, storage units, and other distributed hydraulic structures in order to augment drainage system capacities in a resilient manner.

With the recent heavy snowfalls across Canada, Mohammadiun says the silver lining when it comes to drainage is that it takes snow time to melt whereas heavy rainfall puts an immediate stress on these systems. But from the engineering point of view, it is necessary to consider both acute and chronic conditions.

Not surprising, the research shows that urban  and stormwater systems that are built or modified to be more resilient, will handle  more effectively and efficiently than conventional designs.

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Crystal-stacking process can produce new materials for high-tech devices

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The magnetic, conductive and optical properties of complex oxides make them key to components of next-generation electronics used for data storage, sensing, energy technologies, biomedical devices and many other applications.

Stacking ultrathin complex oxide single-crystal layers — those composed of geometrically arranged atoms — allows researchers to create new structures with hybrid properties and multiple functions. Now, using a new platform developed by engineers at the University of Wisconsin-Madison and the Massachusetts Institute of Technology, researchers will be able to make these stacked-crystal materials in virtually unlimited combinations.

The team published details of its advance Feb. 5 in the journal Nature.

Epitaxy is the process for depositing one material on top of another in an orderly way. The researchers’ new layering method overcomes a major challenge in conventional epitaxy — that each new complex oxide layer must be closely compatible with the atomic structure of the underlying layer. It’s sort of like stacking Lego blocks: The holes on the bottom of one block must align with the raised dots atop the other. If there’s a mismatch, the blocks won’t fit together properly.


“The advantage of the conventional method is that you can grow a perfect single crystal on top of a substrate, but you have a limitation,” says Chang-Beom Eom, a UW-Madison professor of materials science and engineering and physics. “When you grow the next material, your structure has to be the same and your atomic spacing must be similar. That’s a constraint, and beyond that constraint, it doesn’t grow well.”

A couple of years ago, a team of MIT researchers developed an alternate approach. Led by Jeehwan Kim, an associate professor in mechanical engineering and materials science and engineering at MIT, the group added an ultrathin intermediate layer of a unique carbon material called graphene, then used epitaxy to grow a thin semiconducting material layer atop that. Just one molecule thick, the graphene acts like a peel-away backing due to its weak bonding. The researchers could remove the semiconductor layer from the graphene. What remained was a freestanding ultrathin sheet of semiconducting material.

Eom, an expert in complex oxide materials, says they are intriguing because they have a wide range of tunable properties — including multiple properties in one material — that many other materials do not. So, it made sense to apply the peel-away technique to complex oxides, which are much more challenging to grow and integrate.

“If you have this kind of cut-and-paste growth and removal, combined with the different functionality of putting single-crystal oxide materials together, you have a tremendous possibility for making devices and doing science,” says Eom, who connected with mechanical engineers at MIT during a sabbatical there in 2014.

The Eom and Kim research groups combined their expertise to create ultrathin complex oxide single-crystal layers, again using graphene as the peel-away intermediate. More importantly, however, they conquered a previously insurmountable obstacle — the difference in crystal structure — in integrating different complex oxide materials.

“Magnetic materials have one crystal structure, while piezoelectric materials have another,” says Eom. “So you cannot grow them on top of each other. When you try to grow them, it just becomes messy. Now we can grow the layers separately, peel them off, and integrate them.”

In its research, the team demonstrated the efficacy of the technique using materials such as perovskite, spinel and garnet, among several others. They also can stack single complex oxide materials and semiconductors.

“This opens up the possibility for the study of new science, which has never been possible in the past because we could not grow it,” says Eom. “Stacking these was impossible, but now it is possible to imagine infinite combinations of materials. Now we can put them together.”

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New robot does superior job sampling blood

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In the future, robots could take blood samples, benefiting patients and healthcare workers alike.

A Rutgers-led team has created a blood-sampling robot that performed as well or better than people, according to the first human clinical trial of an automated blood drawing and testing device.

The device provides quick results and would allow healthcare professionals to spend more time treating patients in hospitals and other settings.

The results, published in the journal Technology, were comparable to or exceeded clinical standards, with an overall success rate of 87% for the 31 participants whose blood was drawn. For the 25 people whose veins were easy to access, the success rate was 97%.

The device includes an ultrasound image-guided robot that draws blood from veins. A fully integrated device, which includes a module that handles samples and a centrifuge-based blood analyzer, could be used at bedsides and in ambulances, emergency rooms, clinics, doctors’ offices and hospitals.


Venipuncture, which involves inserting a needle into a vein to get a blood sample or perform IV therapy, is the world’s most common clinical procedure, with more than 1.4 billion performed daily in the United States. But clinicians fail in 27% of patients without visible veins, 40% of patients without palpable veins and 60% of emaciated patients, according to previous studies.

Repeated failures to start an IV line boost the likelihood of phlebitis, thrombosis and infections, and may require targeting large veins in the body or arteries — at much greater cost and risk. As a result, venipuncture is among the leading causes of injury to patients and clinicians. Moreover, a hard time accessing veins can increase procedure time by up to an hour, requires more staff and costs more than $4 billion a year in the United States, according to estimates.

“A device like ours could help clinicians get blood samples quickly, safely and reliably, preventing unnecessary complications and pain in patients from multiple needle insertion attempts,” said lead author Josh Leipheimer, a biomedical engineering doctoral student in the Yarmush lab in the biomedical engineering department in the School of Engineering at Rutgers University-New Brunswick.

In the future, the device could be used in such procedures as IV catheterization, central venous access, dialysis and placing arterial lines. Next steps include refining the device to improve success rates in patients with difficult veins to access. Data from this study will be used to enhance artificial intelligence in the robot to improve its performance.

Rutgers co-authors include Max L. Balter and Alvin I. Chen, who both graduated with doctorates; Enrique J. Pantin at Rutgers Robert Wood Johnson Medical School; Professor Kristen S. Labazzo; and principal investigator Martin L. Yarmush, the Paul and Mary Monroe Endowed Chair and Distinguished Professor in the Department of Biomedical Engineering. A researcher at Icahn School of Medicine at Mount Sinai Hospital also contributed to the study.

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Materials provided by Rutgers UniversityNote: Content may be edited for style and length.

Journal Reference:

  1. Josh M. Leipheimer, Max L. Balter, Alvin I. Chen, Enrique J. Pantin, Alexander E. Davidovich, Kristen S. Labazzo, Martin L. Yarmush. First-in-human evaluation of a hand-held automated venipuncture device for rapid venous blood drawsTECHNOLOGY, 2020; 1 DOI: 10.1142/S2339547819500067

Accelerating chemical reactions without direct contact with a catalyst

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“Improving our understanding of the catalyst-intermediary-reaction relationship could greatly expand the possibilities of catalytic reactions,” said Harold Kung, Walter P. Murphy Professor of Chemical and Biological Engineering at the McCormick School of Engineering, who led the research. “By learning that a chemical reaction can proceed without direct contact with a catalyst, we open the door to using catalysts from earth-abundant elements to perform reactions they normally wouldn’t catalyze.”

The study, titled “Noncontact Catalysis: Initiation of Selective Ethylbenzene Oxidation by Au Cluster-Facilitated Cyclooctene Epoxidation,” was published January 31 in the journal Science Advances. Mayfair Kung, a research associate professor of chemical and , was a co-corresponding author on the paper. Linda Broadbelt, Sarah Rebecca Roland Professor of Chemical and Biological Engineering and associate dean for research, also contributed to the study.


The research builds on previous work in which the team investigated the selective oxidation of cyclooctene—a type of hydrocarbon—using gold (Au) as a catalyst. The study revealed that the reaction was catalyzed by dissolved gold nanoclusters. Surprised, the researchers set out to investigate how well the gold clusters could catalyze selective oxidation of other hydrocarbons.

Using a platform they developed called Noncontact Catalysis System (NCCS), the researchers tested the effectiveness of a gold catalyst against ethylbenzene, an organic compound prevalent in the production of many plastics. While ethylbenzene did not undergo any reaction in the presence of the gold clusters, the team found that when the gold clusters reacted with the cyclooctene, the resulting molecule provided the necessary intermediary to produce ethylbenzene oxidation.

Bending diamond at the nanoscale

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The discovery opens up a range of possibilities for the design and engineering of new nanoscale devices in sensing, defence and energy storage but also shows the challenges that lie ahead for future nanotechnologies, the researchers say.

Carbon-based nanomaterials, such as diamond, were of particular scientific and technological interest because, “in their natural form, their mechanical properties could be very different from those at the micro and nanoscale,” said the lead author of the study, published in Advanced Materials, PhD student Blake Regan from the University of Technology Sydney (UTS).

“Diamond is the frontrunner for emerging applications in nanophotonics, microelectrical mechanical systems and radiation shielding. This means a diverse range of applications in medical imaging, temperature sensing and quantum information processing and communication.


“It also means we need to know how these materials behave at the nanoscale — how they bend, deform, change state, crack. And we haven’t had this information for single-crystal diamond,” Regan said.

The team, which included scientists from Curtin University and Sydney University, worked with diamond nanoneedles, approximately 20nm in length, or 10,000 times smaller than a human hair. The nanoparticles were subjected to an electric field force from a scanning electron microscope. By using this unique, non-destructive and reversible technique, the researchers were able to demonstrate that the nanoneedles, also known as diamond nanopillars, could be bent in the middle to 90 degrees without fracturing.

As well as this elastic deformation, the researchers observed a new form of plastic deformation when the nanopillar dimensions and crystallographic orientation of the diamond occurred together in a particular way.

Chief Investigator UTS Professor Igor Aharonovich said the result was the unexpected emergence of a new state of carbon (termed 08-carbon) and demonstrated the “unprecedented mechanical behaviour of diamond.”

“These are very important insights into the dynamics of how nanostructured materials distort and bend and how altering the parameters of a nanostructure can alter any of its physical properties from mechanical to magnetic to optical. Unlike many other hypothetical phases of carbon, 08-carbon appears spontaneously under strain with the diamond-like bonds progressively breaking in a zipper-like manner, transforming a large region from diamond into 08-carbon.

“The potential applications of nanotechnology are quite diverse. Our findings will support the design and engineering of new devices in applications such as super-capacitors or optical filters or even air filtration,” he said.

Induced flaws in metamaterials can produce useful textures and behaviour

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A new Tel Aviv University study shows how induced defects in metamaterials — artificial materials the properties of which are different from those in nature — also produce radically different consistencies and behaviors. The research has far-reaching applications: for the protection of fragile components in systems that undergo mechanical traumas, like passengers in car crashes; for the protection of delicate equipment launched to space; and even for grabbing and manipulating distant objects using a small set of localized manipulations, like minimally invasive surgery.


“We’ve seen non-symmetric effects of a topological imperfection before. But we’ve now found a way to create these imperfections in a controlled way,” explains Prof. Yair Shokef of TAU’s School of Mechanical Engineering, co-author of the new study. “It’s a new way of looking at mechanical metamaterials, to borrow concepts from condensed-matter physics and mathematics to study the mechanics of materials.”

The new research is the fruit of a collaboration between Prof. Shokef and Dr. Erdal O?uz of TAU and Prof. Martin van Hecke and Anne Meeussen of Leiden University and AMOLF in Amsterdam. The study was published in Nature Physics on January 27. “Since we’ve developed general design rules, anyone can use our ideas,” Prof. Shokef adds.

“We were inspired by LCD-screens that produce different colors through tiny, ordered liquid crystals,” Prof. Shokef says. “When you create a defect — when, for example, you press your thumb against a screen — you disrupt the order and get a rainbow of colors. The mechanical imperfection changes how your screen functions. That was our jumping off point.”

The scientists designed a complex mechanical metamaterial using three-dimensional printing, inserted defects into its structure and showing how such localized defects influenced the mechanical response. The material invented was flat, made out of triangular puzzle pieces with sides that moved by bulging out or dimpling in. When “perfect,” the material is soft when squeezed from two sides, but in an imperfect material, one side of the material is soft and the other stiff. This effect flips when the structure is expanded at one side and squeezed at the other: stiff parts become soft, and soft parts stiff.

“That’s what we call a global, topological imperfection,” Prof. Shokef explains. “It’s an irregularity that you can’t just remove by locally flipping one puzzle piece. Specifically, we demonstrated how we can use such defects to steer mechanical forces and deformations to desired regions in the system.”

The new research advances the understanding of structural defects and their topological properties in condensed-matter physics systems. It also establishes a bridge between periodic, crystal-like metamaterials and disordered mechanical networks, which are often found in biomaterials.

The research team plans to continue their research into three-dimensional complex metamaterials, and to study the richer geometry of imperfections there.