Such is the case with a hybrid microscope, born at the Marine Biological Laboratory (MBL), that for the first time allows scientists to simultaneously image the full 3D orientation and position of an ensemble of molecules, such as labeled proteins inside cells. The research is published this week in Proceedings of the National Academy of Sciences.

The microscope combines polarized fluorescence technology, a valuable tool for measuring the orientation of molecules, with a dual-view light sheet microscope (diSPIM), which excels at imaging along the depth (axial) axis of a sample.

This scope can have powerful applications. For example, proteins change their 3D orientation, typically in response to their environment, which allows them to interact with other molecules to carry out their functions.

“Using this instrument, 3D protein orientation changes can be recorded,” said first author Talon Chandler of CZ Biohub San Francisco, a former University of Chicago graduate student who conducted this research partly at MBL. “There’s real biology that might be hidden to you from just a position change of a molecule alone,” he said.

Imaging the molecules in the spindle of a dividing cell — a longstanding challenge at MBL and elsewhere — is another example.

“With traditional microscopy, including polarized light, you can study the spindle quite nicely if it’s in the plane perpendicular to the viewing direction. As soon as the plane is tilted, the readout becomes ambiguous,” said co-author Rudolf Oldenbourg, a senior scientist at MBL. This new instrument allows one to “correct” for tilt and still capture the 3D orientation and position of the spindle molecules (microtubules).

The team hopes to make their system faster so that they can observe how the position and orientation of structures in live samples change over time. They also hope development of future fluorescent probes will enable researchers to use their system to image a greater variety of biological structures.

A Confluence of Vision

The concept for this microscope gelled in 2016 through brainstorming by innovators in microscopy who met up at the MBL.

Hari Shroff of HHMI Janelia, then at the National Institutes of Health (NIH) and an MBL Whitman Fellow, was working with his custom-designed diSPIM microscope at MBL, which he built in collaboration with Abhishek Kumar, now at MBL.

The diSPIM microscope has two imaging paths that meet at a right angle on the sample, allowing researchers to illuminate and image the sample from both perspectives. This dual view can compensate for the poor depth resolution of any single view, and illuminate with more control over polarization than other microscopes.

In conversation, Shroff and Oldenbourg realized the dual view microscope could also address a limitation of polarized light microscopy, which is that it’s difficult to efficiently illuminate the sample with polarized light along the direction of light propagation.

“If we had two orthogonal views, we could sense polarized fluorescence along that direction much better,” Shroff said. “We thought, why not use the diSPIM to take some polarized fluorescence measurements?”

Shroff had been collaborating at MBL with Patrick La Rivière, a professor at University of Chicago whose lab develops algorithms for computational imaging systems. And La Rivière had a new graduate student in his lab, Talon Chandler, whom he brought to MBL. The challenge of combining these two systems became Chandler’s doctoral thesis, and he spent the next year in Oldenbourg’s lab at MBL working on it.

The team, which early on included Shalin Mehta, then based at MBL, outfitted the diSPIM with liquid crystals, which allowed them to change the direction of input polarization.

“And then I spent a long time working through, what would a reconstruction look like for this? What is the most we can recover from this data that we are now starting to acquire?” Chandler said. Co-author Min Guo, then located at Shroff’s previous lab at NIH, also worked tirelessly on this aspect, until they had reached their goal of full 3D reconstructions of molecular orientation and position.

“There was tons of cross-talk between the MBL, the University of Chicago, and the NIH, as we worked this through,” Chandler said.

“The results show that glass fertilizers can be tailored to plant needs, slowly and sustainably releasing nutrients to boost productivity without harming soil quality,” says Danilo Manzani, a co-author of the study.

Over time, the use of agricultural chemicals has increased. In 2020, the Food and Agriculture Organization of the United Nations estimated that global demand for fertilizers would surpass 200 million metric tonnes. Fertilizers contain nitrogen, phosphorus and lower amounts of other elements like calcium. Unfortunately, the benefits of these nutrients are lost through leaching into groundwater and emissions into the air, necessitating frequent reapplication and creating downstream environmental problems like toxic algal blooms. A potential solution could come from tiny glass beads that previous researchers used to improve plant growth. To improve the efficiency of nutrient delivery, Manzani, Eduardo Ferreira and colleagues developed a water-soluble, multicomponent glass fertilizer designed for controlled nutrient release.

The researchers synthesized glass consisting of several micro- and macronutrients, such as phosphorus, potassium and calcium. They ground the glass into small (less than 0.85 millimeters wide) and large (0.85 to 2 millimeters wide) particles. In an initial test, the particles were added to either water or a buffer solution that mimicked soil conditions. They found that each nutrient released from both sizes of glass particles and diffused into the solutions steadily over 100 hours with minor fluctuations.

They then applied a nutrient solution or different amounts of the glass beads to soil seeded with a typical lawn and fairway grass, and they compared the plants’ growth in the two treatments. The nutrient solution, which was applied only once, immediately stimulated plant growth, but the effect quickly diminished. However, the single application of glass fertilizer sustained plant growth regardless of particle size, though overall growth depended on the bead dose.

Manzani, Ferreira and colleagues also examined the possible ecotoxicity of the glass fertilizer by exposing lettuce and onion seeds to the beads. Seeds exposed to glass fertilizer had roughly the same germination rate and cell health as those never exposed or those treated with soluble nutrients. The researchers say that these results indicate an efficient and sustained alternative to conventional fertilizers with lower environmental impact.

The authors acknowledge funding from the São Paulo Research Foundation; Center for Research, Technology, and Education in Vitreous Materials; National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico); Coordination for the Improvement of Higher Education Personnel; and Funding Authority for Studies and Projects.

Hair conditioners typically contain 20-30 ingredients, many derived from petroleum and oleochemicals, raising concerns about sustainability and environmental impact. A new study published in Science Advances, demonstrates that micellar lignin gels can effectively stabilize emulsions with natural oils, reducing the need for synthetic surfactants and complex stabilizers commonly used in commercial formulations. The research team, led by Mika Sipponen at Stockholm University, sought to explore lignin, a common and renewable component in wood biomass, as a multifunctional component for hair conditioning.

“Our findings highlight lignin’s potential as a stabilizer in oil-in-water emulsions, enabling a more natural and sustainable approach to hair conditioning,” says Mika Sipponen. “By using wood-derived lignin directly without any chemical modification, we not only simplify the ingredient list but also eliminate the need for organic solvents, making the process more eco-friendly.”

Comparable to commercial hair conditioners

The lignin gel-based conditioner was tested against a commercial hair conditioner, showing comparable emulsion stability, viscosity, and conditioning performance. A formulation with 6 percent coconut oil effectively lubricated damaged hair, reducing wet combing force by 13 percent, as confirmed by combing force measurements and multiscale microscopy analysis. Importantly, the product was easily rinsed off from paper and skin with cold water despite its dark color, demonstrating practical usability.

New opportunities in cosmetics and food

Ievgen Pylypchuk, who has been instrumental in developing lignin gel as a versatile platform material, highlights its broader potential: “Our lignin gel technology extends beyond personal care applications. Its unique ability to stabilize emulsions and interact with various biomolecules opens opportunities in cosmetics, food, and even biomedical formulations, offering a sustainable alternative to conventional ingredients.”

This innovation paves the way for greener haircare solutions that align with growing consumer demand for sustainable personal care products. The researchers anticipate further exploration of lignin-based formulations for broader applications in the personal care industry.