Sunday, March 10, 2024

 

New dual therapeutic strategy shows promise against multidrug-resistant salmonella


Peer-Reviewed Publication

UNIVERSITY OF EASTERN FINLAND

Proposed model for CA439-colistin potentiation. 

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QUINAZOLINE CA439 ENHANCES THE ACTION OF THE ANTIMICROBIAL PEPTIDE COLISTIN THROUGH A TRIPLE MECHANISM OF ACTION THAT INVOLVES: 1, PERMEABILIZATION OF THE BACTERIAL OUTER MEMBRANE; 2, DOWN-REGULATION OF POLYMYXIN RESISTANCE GENES THROUGH THE PHOP/PHOQ-PMRA/PMRB CASCADE; 3, ALTERATION OF ELECTROCHEMICAL POTENTIAL OF THE BACTERIAL INNER MEMBRANE.

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CREDIT: C. ASQUITH.




A new collaborative study discloses the discovery and application of a new therapeutic strategy to target the multidrug-resistant bacterium Salmonella enterica in vivo, with promising results. The results were published in Scientific Reports.

The study was carried out by researchers from the University of Eastern Finland, as well as from the Rosario National University, Argentina, and the University of the Republic, Uruguay.

Antibiotic-resistant bacterial infections stand as one of the critical biological threats to human health on a global scale, exemplified by the multidrug-resistant (MDR) Salmonella enterica. The rise of MDR strains, coupled with the constrained array of treatment options, necessitates the innovation of therapeutic approaches. Addressing this imperative, the study introduces a strategy to enhance the efficacy of colistin, a last-resort antibiotic.

“Through the utilisation of a non-antibiotic anti-virulence quinazoline compound, we investigated a dual-pronged therapeutic methodology,” explains Senior Researcher Christopher Asquith from the School of Pharmacy at the University of Eastern Finland.

In an earlier study, the team had discovered a quinazoline compound suitable for this purpose.

The combined treatment with the quinazoline and colistin targets Salmonella by simultaneously inhibiting its resistance mechanisms against colistin and disrupting the bacterium's envelope electrochemical equilibrium. This synergistic interplay not only introduces a new route to counter MDR bacteria but also lays the groundwork for potentially addressing resistance challenges associated with other antibiotics.

The quinazoline compound specifically affected the Salmonella PhoP/PhoQ two-component signal transduction cascade, which is a key regulatory pathway exploited by this pathogen for both the advancement of infection and the development of resistance. The outcomes presented within this study underscore the potential of leveraging this pathway to target bacterial disease. It also provides a blueprint for tailored interventions beyond Salmonella to a spectrum of bacterial infections.

The efficacy of the dual treatment in mitigating mortality within an in vivo insect infection model marks a stride toward potential therapeutic applications.

“Collectively, these findings hold implications for combating antibiotic resistance and deepening our comprehension of bacterial pathogenesis. The prospective to reshape treatment strategies and alleviate the global burden of MDR infections make this work a significant contribution to the antimicrobial research field,” Asquith says.

 

Paper coating biomaterials derived from anaerobic granular sludge may be cost-effective


Peer-Reviewed Publication

EURASIA ACADEMIC PUBLISHING GROUP




The demand for paper and paperboard production continuously grows worldwide, particularly in the packaging industry. Due to the paper's nature, it usually requires a surface coating to keep out water, oil, and other unwanted substances. These coatings can come with high financial and environmental costs. Using renewable coating materials that are also cost-effective can support sustainability strategies.

 

A promising new technique using extracellular polymeric substances (EPS) recovered from anaerobic granular sludge may offer a cost-effective, sustainable approach for transforming wastewater into industrially valuable products, and help to reduce carbon emissions.

 

In a study published in Environmental Science and Ecotechnology, researchers coated paper using EPS extracted from various anaerobic granules in wastewater. This approach enhanced waterproofing (65%), as well as oil and grease resistance, while the multi-layered microstructure of the coated paper exhibited a smoother and less porous surface overall. Extracellular proteins, abundant in β-sheets and random coils, play a pivotal structural role in paper coating.

 

Biological treatment based on activated sludge has been the most widely used approach in removing major pollutants from wastewater. However, excess sludge disposal accounts for up to 50% of wastewater treatment costs and presents a significant challenge in wastewater treatment. Wastewater treatment plants are shifting to recovering raw materials, turning these into potential renewable sources. Excess sludge, rich in EPS, is becoming increasingly attractive and contributes to implementing the “biorefinery” paradigm from wastewater treatment plants. EPS-based biomaterials are potential alternatives to synthetic polymers in various applications, such as agriculture, medical, and construction industries, as they have polysaccharides, proteins, and humic-acid substances.

 

In this study, anaerobic granules were collected from a brewery wastewater treatment plant and a paper-industry wastewater treatment plant. Regardless of the different sludge sources, EPS from both types were mainly composed of proteins. EEM spectra confirmed that tryptophan or protein-like components were the dominant substances, together with humic-like components.

 

The addition of EPS resulted in improved water/grease-proofing behaviour. The best results were achieved with the EPS samples from paper-industry sludge, characterised by a higher fraction of proteins and hydrophobic contents than the other EPS samples. Moreover, the extracellular proteins rich in β-sheets and random coil would facilitate a structural role for paper coating.

 

This research establishes for the first time that EPS derived from anaerobic granules exhibits interesting water barrier properties when used as paper coating additives. More importantly, from the paper industry's perspective, these EPS enhance resistance to grease penetration and absorbance. These biomaterials recovered from waste granular sludge provide a sustainable resource for industrial application and promise to realise a sustainable and circular economy.

 

 

Disorders of consciousness: Increasing awareness of advances in brain injury medicine


A themed issue of NeuroRehabilitation not only offers cutting-edge information on disorders of consciousness, but just as importantly, hope for improved diagnosis, treatment, and patient outcomes


Peer-Reviewed Publication

IOS PRESS




Amsterdam, March 7, 2024 – Emerging trends and new developments in the care and management of patients with disorders of consciousness (DoC) are increasingly focused on a multidisciplinary approach that integrates evidence-based assessment, treatment, and ethical aspects. A themed issue of the journal NeuroRehabilitation, published by IOS Press, outlines advances in nosology and classification, understanding of covert consciousness and its assessment, neuromedical morbidity and prognostication, neurorehabilitation evaluation and treatment, use of neurotechnologies in assessment and treatment, as well as medicolegal and ethical challenges

Patients with severe brain injuries with DoC, such as coma, unresponsive wakefulness syndrome, and minimally conscious state, have better prognoses than previously believed, but each case is unique and requires careful assessment due to a high rate of misdiagnosis.

This compilation of articles from highly regarded experts in the field highlights a wide range of topics on the current state of our knowledge regarding DoC including nomenclature, diagnosis and prognosis, assessment techniques (such as behavioral scales, multi-modal assessment, and brain-computer interface), clinical management, and ethical as well as medicolegal issues. The outlook for neurological as well as functional recovery and improved quality of life are also covered.

"The development of novel rehabilitation treatments (particularly, neuromodulation and open label drugs), targeting specific brain areas or networks that are known to be key in consciousness recovery offers exciting hope for advancement of treatment approaches in persons with DoC," says co-Guest Editor of the issue Caroline Schnakers, PhD, Assistant Director of the Research Institute at Casa Colina Hospital and Centers for Healthcare, Pomona, CA.

An increasing number of studies on long-term outcomes emphasize the potential for neurorehabilitation and neuroplasticity to promote recovery and improve outcomes in these patients. There is a growing emphasis on utilizing advanced assessment techniques, such as neuroimaging (e.g., functional MRI, PET scans) and electrophysiological methods (e.g., EEG, evoked potentials), to improve assessment of consciousness.

To enhance communication and interaction for patients with severe communication impairments due to DoC, technological advancements, such as brain-computer interfaces and assistive devices, are being explored as potential tools. This has the potential to accurately diagnose and assess the level of consciousness in patients with DoC, especially those who may have covert consciousness.

The article “Prognosis and enhancement of recovery in disorders of consciousness reviews the challenges faced by medical professionals, researchers, and families who must make decisions about a patient with DoC—important decisions that require certainty. The authors provide an overview of the current clinical landscape surrounding prognosis and optimizing recovery in DoC and the current and future research that could improve prognostic accuracy after severe brain injury. Improved understanding of these factors will aid healthcare professionals in providing optimal care, fostering hope, and advocating for ethical practices in the management of individuals with DoC.

Advocating for the rights of patients with DoC will be crucial to providing the best chances for optimizing rehabilitation outcomes. The issue also highlights the ramifications for attorneys involved with brain injury neurolitigation. They may be involved in cases in which civil rights of individuals with DoC are at stake, requiring an in-depth understanding of the legal and ethical framework surrounding these issues. It is therefore critical for attorneys to remain engaged with advances in the field of DoC neuroscience and neurorehabilitation to advocate for their clients (whether in a plaintiff or defense context). 

The article “Brain injury, medical progress, and the disability paradox: Towards an Americans with Abilities Act assesses limitations to current disability law that contribute to ongoing segregation and marginalization of individuals with severe brain injury, and proposes instead to complement current legislation with the Americans with Abilities Act (AWAA). Instead of focusing on disabilities that need protection, the AWAA seeks to sustain and foster newfound abilities made possible by the fruits of medicine and neuroscience.

 

Co-Guest Editor Nathan Zasler, MD, DAAPM&R, FAAPM&R, FACRM, BIM, Concussion Care Centre of Virginia and Tree of Life (Richmond), Department of Physical Medicine and Rehabilitation at both Virginia Commonwealth University and University of Virginia (Charlottesville), adds, "Overall, there has been collaborative research initiatives and networks that have recently been established to facilitate the sharing of data, resources, and expertise in the field of DoC research, leading to a more coordinated and impactful approach to advancing knowledge and improving patient care."

Such advances in neurorehabilitation care are expected to lead to more tailored and effective treatments that may be driven by more personalized, multimodal assessment protocols. Access to specialized care and resources for patients with DoC can be limited, especially in some geographic areas or healthcare systems. It is therefore essential to advocate for improved access to care, as well as the development of telemedicine and other remote monitoring solutions to overcome such barriers.

There remain significant challenges to optimal diagnosis and care, but ongoing progress in research, technology, ethics, and interdisciplinary collaboration holds promise for improving the assessment, treatment, and outcomes of patients with DoC.

“Finally, there is still a lack of awareness and understanding of DoC among healthcare professionals and the public at large, which can contribute to stigma and misconceptions that only promulgate suboptimal clinical decisions and ultimately suboptimal care,” Dr. Schnakers concludes. “Maintaining (and intensifying) current public education campaigns and advocacy efforts will raise more awareness about patients with DoC and promote empathy as well as support for affected individuals and their families.”

 

 

Veteran PTSD fishing treatment project nets $1.3m in funding


Grant and Award Announcement

UNIVERSITY OF ESSEX

Dr Nick Cooper 

IMAGE: 

DR NICK COOPER

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CREDIT: UNIVERSITY OF ESSEX




A “game-changing” $1.3m cash injection has been awarded to researchers exploring if doctors can prescribe fishing to treat PTSD.  

The vital funding will allow the University of Essex’s Dr Nick Cooper and collaborator Dr Mark Wheeler to expand their influential work which has helped hundreds of military veterans.  

Now the Department of Psychology’s Dr Cooper will explore if casting a rod from the bankside can aid police officers, paramedics, firefighters, and the coast guard deal with trauma.    

Taking place over the course of three and a half years the National Institute for Health and Care Research-funded project (NIHR) is one of only three being explored across the UK.  

It is hoped Casting Away Trauma will develop innovative nature-based treatments for mental health conditions on the NHS.  

Watch a YouTube documentary on the project's life-changing work here.

Dr Cooper said: “This is a game-changing funding for our research, which will help us show definitively if fishing can make a real difference to the people who have given so much to keep us all safe.  

“We are incredibly proud to receive NIHR funding to expand our project, which we have proved has a real impact on servicemen and women. 

“We have shown that a weekend of angling has demonstrable and real impact on vulnerable veterans and can help them back into society. 

“We are incredibly excited and honoured to receive the funding to expand our research.” 

PTSD -Post Traumatic Stress Disorder - sees sufferers relive traumatic and can lead to debilitating depression, anxiety and even suicide. 

The Casting Away Trauma project has found a way to break barriers stopping veterans and other sufferers from engaging with traditional therapy. 

By emphasising learning a new recreational skill rather than traditional therapy they use peer support and sessions led by a qualified recreation coach to ease the symptoms. 

Dr Wheeler added: “This is a tremendous piece of news for all concerned.  

“As joint CEO of iCARP CIC, alongside Dr Cooper, I can state that, as an organisation, we are immensely proud to have played our part in this ground-breaking research project.  

“From our first research design and trip, 10 years ago now, we have worked tirelessly to reach this point and could not be more pleased for all our supporters, collaborators and volunteers who have all played an integral part in the programme.  

“We look forward to the next part of the journey with excitement and anticipation. 

Dr Cooper and Dr Wheeler will conduct the research through their community interest company iCARP CIC, which runs picturesque lakes nestled near Harwich, Essex.” 

Their previous research took servicemen with PTSD, who had an average of 12 years military experience on a weekend fishing retreat – focussing on relaxation, socialisation and learning new skills. 

The innovative intervention sparked significant clinical change in 60% of participants that also reduced depression and anxiety for a month after the trip – with wellbeing scores soaring. 

It also confirmed the 30-hour, 2-day peer-support intervention can now be expanded to deliver a large-scale trial using the same methods. 

The project has been praised by the Ministry of Defence (receiving a gold award in 2022), recognised by The Angling Trust and recently received a contract to deliver community mental health treatment for the NHS Essex Partnership University Trust via local volunteering bodies. 

Veteran Brian Haycock fishing


 

The who's who of bacteria: A reliable way to define species and strains


Peer-Reviewed Publication

GEORGIA INSTITUTE OF TECHNOLOGY

The Who's Who of Bacteria: A Reliable Way to Define Species and Strains 

IMAGE: 

THE SALTERN SITE IN SPAIN WHERE A SIGNIFICANT PORTION OF THE RESEARCH WAS DONE. A SALTERN IS USED TO PRODUCE SALT FOR HUMAN CONSUMPTION AND IS A NATURAL ENVIRONMENT FOR SALINIBACTER RUBER BACTERIUM.

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CREDIT: TOMEU VIVER, MEDITERRANEAN INSTITUTES FOR ADVANCED STUDIES AND THE MAX PLANCK INSTITUTE




What’s in a name? A lot, actually.

For the scientific community, names and labels help organize the world’s organisms so they can be identified, studied, and regulated. But for bacteria, there has never been a reliable method to cohesively organize them into species and strains. It’s a problem, because bacteria are one of the most prevalent life forms, making up roughly 75% of all living species on Earth.

An international research team sought to overcome this challenge, which has long plagued scientists who study bacteria. Kostas Konstantinidis, Richard C. Tucker Professor in the School of Civil and Environmental Engineering at the Georgia Institute of Technology, co-led a study to investigate natural divisions in bacteria with a goal of determining a scientifically viable method for organizing them into species and strains. To do this, the researchers let the data show them the way.

Their research was published in the journal Nature Communications.

“While there is a working definition for species and strains, this is far from widely accepted in the scientific community,” Konstantinidis said. “This is because those classifications are based on humans’ standards that do not necessarily translate well to the patterns we see in the natural environment.”

For instance, he said, “If we were to classify primates using the same standards that are used to classify E. coli, then all primates — from lemurs to humans to chimpanzees — would belong to a single species.”

There are many reasons why a comprehensive organizing system has been hard to devise, but it often comes down to who gets the most attention and why. More scientific attention generally leads to those bacteria becoming more narrowly defined. For example, bacteria species that contain toxic strains have been extensively studied because of their associations with disease and health. This has been out of the necessity to differentiate harmful strains from harmless ones. Recent discoveries have shown, however, that even defining types of bacteria by their toxicity is unreliable.

“Despite the obvious, cornerstone importance of the concepts of species and strains for microbiology, these remain, nonetheless, ill-defined and confusing,” Konstantinidis said.

The research team collected bacteria from two salterns in Spain. Salterns are built structures in which seawater evaporates to form salt for consumption. They harbor diverse communities of microorganisms and are ideal locations to study bacteria in their natural environment. This is important for understanding diversity in populations because bacteria often undergo genetic changes when exposed in lab environments.

The team recovered and sequenced 138 random isolates of Salinibacter ruber bacteria from these salterns. To identify natural gaps in genetic diversity, the researchers then compared the isolates against themselves using a measurement known as average nucleotide identity (ANI) — a concept Konstantinidis developed early in his career. ANI is a robust measure of relatedness between any two genomes and is used to study relatedness among microorganisms and viruses, as well as animals. For instance, the ANI between humans and chimpanzees is about 98.7%.

The analysis confirmed the team’s previous observations that microbial species do exist and could be reliably described using ANI. They found that members of the same species of bacteria showed genetic relatedness typically ranging from 96 to 100% on the ANI scale, and generally less than 85% relatedness with members of other species.

The data revealed a natural gap in ANI values around 99.5% ANI within the Salinibacter ruber species that could be used to differentiate the species into its various strains. In a companion paper published in mBio, the flagship journal of the American Society for Microbiology, the team examined about 300 additional bacterial species based on 18,000 genomes that had been recently sequenced and become available in public databases. They observed similar diversity patterns in more than 95% of the species.

“We think this work expands the molecular toolbox for accurately describing important units of diversity at the species level and within species, and we believe it will benefit future microdiversity studies across clinical and environmental settings,” Konstantinidis said.

The team expects their research will be of interest to any professional working with bacteria, including evolutionary biologists, taxonomists, ecologists, environmental engineers, clinicians, bioinformaticians, regulatory agencies, and others. It is available online through Konstantinidis’ website and GitHub to facilitate access and use by scientific and regulatory communities.

“We hope that these communities will embrace the new results and methodologies for the more robust and reliable identification of species and strains they offer, compared to the current practice,” Konstantinidis said.

A microscopy photo of Salinibacter ruber, a bacterium that thrives in salterns.

CREDIT

Tomeu Viver, Mediterranean Institutes for Advanced Studies and the Max Planck Institute

Note: Tomeu Viver (Mediterranean Institutes for Advanced Studies and Max Planck Institute) and Ramon Rossello-Mora (Mediterranean Institutes for Advanced Studies) also led the research. Additional researchers from the Georgia Institute of Technology, University of Innsbruck, University of Pretoria, University of Las Palmas de Gran Canaria, University of the Balearic Islands, and the Max Planck Institute also contributed. 

Citation: Viver, T., Conrad, R.E., Rodriguez-R, L.M. et al. Towards estimating the number of strains that make up a natural bacterial population. Nat Commun 15, 544 (2024).

DOIhttps://doi.org/10.1038/s41467-023-44622-z

Funding: Spanish Ministry of Science, Innovation and Universities, European Regional Development Fund, U.S. National Science Foundation.

Writer: Catherine Barzler, Georgia Institute of Technology

A screenshot from a team meeting. The study's international team has researchers based in the U.S., Spain, Germany, Austria, and South Africa.

CREDIT

Kostas Konstantinidis, Georgia Institute of Technology

 

Series of important achievements in the scientific investigation of the Yarlung Tsangbo Grand Canyon


Peer-Reviewed Publication

INSTITUTE OF ATMOSPHERIC PHYSICS, CHINESE ACADEMY OF SCIENCES

Comprehensive observation network of water vapor channels in the Yarlung Tsangbo Grand Canyon 

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COMPREHENSIVE OBSERVATION NETWORK OF WATER VAPOR CHANNELS IN THE YARLUNG TSANGBO GRAND CANYON

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CREDIT: XUELONG CHEN




The Second Tibetan Plateau Scientific Expedition and Research Program (STEP) established a scientific expedition team for the water vapor channel of the Yarlung Tsangbo Grand Canyon in the southeast of the Tibetan Plateau. In the past five years, the expedition team has conducted observations and research on water vapor transport and heavy precipitation around the Yarlung Tsangbo Grand Canyon.

 

The expedition team has used the observational data to achieve a series of important scientific achievements. Recently, Atmospheric and Oceanic Science Letters published a review article on the research progress of the Yarlung Zsangbo Grand Canyon water vapor channel. Specifically, the article reports the research progress on heavy rainfall processes related to water vapor transport in the Grand Canyon.

 

The first author of the article, Prof. Chen Xuelong from the Institute of Tibetan Plateau Research, Chinese Academy of Sciences, explains that the rainfall observation network established by his team in the Grand Canyon can represent the spatial impact of the terrain on hourly precipitation in the region. The microphysical characteristics of precipitation in the southeastern Tibetan Plateau are significantly different from those in low-altitude areas, further confirming the unsuitability of cloud microphysical parameterizations in current precipitation numerical models for the Tibetan Plateau region.

 

Satellite-measured precipitation data may provide new insights into the spatial distribution of mountain precipitation, but the results of the investigation team have shown that there is a problem in the form of a dry bias in GPM satellite precipitation data in the Grand Canyon region, and calibration is required before use. The Yarlung Zsangbo Grand Canyon, as an important water vapor source for the Tibetan Plateau, has not been fully understood in previous studies regarding its impact on the precipitation of the Tibetan Plateau. Thus, the article also provides a quantitative analysis of the impact of meridional water vapor transport passing through the Grand Canyon on the precipitation of the Tibetan Plateau. On this basis, it is found that the decrease in precipitation over the southeastern Tibetan Plateau may be due to the decrease in meridional water vapor flux passing through the Grand Canyon.

 

The simulation of mountainous heavy precipitation has always been a difficult task in the precipitation forecasting community. As such, researchers in the expedition team used a numerical model and the established observational network data to test the advantages and disadvantages of different cloud precipitation schemes.

 

“The results showed that only when a 1-km resolution numerical model using specific cloud precipitation and terrain drag parameterization schemes is used can the wind field and water vapor transport in the Grand Canyon be captured. The model can make accurate predictions of nighttime heavy precipitation in the region, and this work provides an important reference for precipitation forecasting in mountainous regions,” explains the corresponding author, Prof. Xuelong Chen.

 

 

How water guides the assembly of collagen, the building block of all humans


Peer-Reviewed Publication

UNIVERSITEIT VAN AMSTERDAM

Artist's impression of the structure of collagen 

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ARTIST'S IMPRESSION OF THE STRUCTURE OF COLLAGEN, CONSISTING OF SINGLE PROTEINS THAT ASSEMBLE INTO FIBRILS, WHICH BUNDLE INTO NETWORKS THAT FORM THE SCAFFOLDS FOR OUR TISSUES. IMAGE: HIMS / LAURA CANIL, GIULIA GIUBERTONI.

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CREDIT: HIMS / LAURA CANIL, GIULIA GIUBERTONI.




Water determines life: humans are three-quarters water. An international research team led by the University of Amsterdam (UvA) has now discovered how water also determines the structure of the material that holds us together: collagen. In a paper recently published in PNAS, the researchers elucidate the role of water in the molecular self-assembly of collagen. They show that by replacing water with its ‘twin molecule’ heavy water (D2O), one can ‘tune’ the interaction between collagen molecules, and thus influence the process of collagen self-assembly. The findings will help to better understand the tissue failures resulting from heritable collagen-related diseases, such as brittle bone disease (osteogenesis imperfecta).

As lead author Dr Giulia Giubertoni of the UvA’s Van ’t Hoff Institute for Molecular Sciences (HIMS) puts it: ‘In studying these and other collagen diseases, many researchers, including myself,  myself have always missed an important part of the puzzle, and the possibility that tissue failure might be partly due to water-collagen interaction was not taken very seriously. We now show that perturbing the water layer around the protein, even very slightly, has dramatic effects on collagen assembly.’

Giubertoni wants to make researchers in the collagen-disease community aware that very subtle changes in the water-collagen interaction might contribute to collagen diseases. These changes can potentially arise, for instance, from mutations in the collagen protein which occur in genetic diseases. The researchers also suggest that altered interactions between water and collagen are a contributing factor in various age-related diseases involving tissue dysfunction.

The stuff we're made of

Collagen is to a large extent ‘the stuff we're made of’- around a third of all protein in our body is collagen which ensures the mechanical integrity of all human connective tissue. For instance, our skin and arteries stretch without tearing and our bones can resist high stress without breaking. Collagen is produced by our cells as single proteins that assemble into larger structures called fibrils. These fibrils further assemble into networks that form the scaffolds for our tissues.

Since collagen is formed in the aqueous environment of human cells, water plays a crucial role in its assembly. The interaction of water molecules with proteins results in collagen that is best suited for its function. But what exactly is behind this collagen-optimising role of water? How does water do it? And will understanding this mechanism offer insights into conditions where something is wrong with collagen, such as osteogenesis imperfecta? These were the central questions of the research now published in PNAS.

Introducing heavy water

To investigate the role of water in collagen formation, Giubertoni - together with her UvA colleague Prof. Sander Woutersen and their collaborator Prof. Gijsje Koenderink (Delft University of Technology) - decided to replace water with its heavier ‘twin molecule’ D2O. Initially discovered by the Nobel prize winner Harold Urey in 1931, in D2O the hydrogen atoms (H) of water are replaced with the isotope deuterium (D) that has an added neutron in its nucleus. D2O or ‘heavy water’ thus is the ‘closest replacement’ to ordinary water in nature.

However, in interaction with proteins, D2O is less potent than H2O. This is because bonds between D2O molecules (so-called hydrogen-bonds) are stronger than those between H2O molecules. This affects the interaction with proteins such as collagen.

Giubertoni, Woutersen and Koenderink were keen to study the effect this would have on collagen assembly. Together with a multi-disciplinary collaborative research network, they were able to establish that the use of heavy water results in ten times faster collagen formation, and ultimately a less homogeneous, softer and less stable collagen-fibre network.

A very effective moderator

The explanation is that the reduced interaction of the heavy water with the collagen protein makes it easier for the protein to ‘shake off’ the D2O molecules and reorganise itself.

This boosts the formation of the collagen network, but also results in a sloppier, less optimal collagen network. Water thus acts as a mediator between collagen molecules, slowing down the assembly to guarantee the functional properties of living tissues.

This discovery offers fresh perspectives on how water influences the characteristics of collagen, allowing for precise adjustments in the mechanical properties of living tissues. It also creates novel avenues for creating collagen-based materials where macroscopic properties can be controlled and fine-tuned by subtle variations in the composition of the solvent, rather than making significant changes to the chemical structure of the molecular building blocks. 

A similar “investigative” approach might be also used in the future to elucidate the role of water in driving and guiding the assembly of other proteins capable of assembling in larger structures. Giubertoni . Giubertoni will move on to study how defects in collagen affect its interaction with water, and what role this plays in the failure of tissue in collagen diseases.

A multi-disciplinary collaborative network

Dr Giulia Giubertoni is a postdoctoral research fellow working towards the molecular understanding of the functionalities of biomolecules and the mechanical properties of biomaterials, in particular skin and bones. In 2021 she was awarded a Veni grant by the Dutch Research Council (NWO) to study the molecular origin of osteogenesis imperfecta. Together with Prof. Sander Woutersen (HIMS, Molecular Photonics), Prof. Gijsje Koenderink (Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology), and her previous Master's student Liru Feng, she established a multidisciplinary, international network of collaborators with complementary expertise ranging from computer simulations to protein imaging and rheology. Together they tackled the collagen research question from molecular to macroscopic level and at different time scales. Collaborators include: Dr Federico Caporaletti (Molecular Photonics HIMS, IoP and Université libre de Bruxelles, Belgium),  Dr Ioana M. Ilie (Computational Chemistry, HIMS), Prof. Daniel Bonn (IoP),  Dr Antoine Deblais (IoP), Dr Johannes Hunger (Max Planck Institute for Polymer Research, Mainz, Germany), Prof. Andela Saric (Institute of Science and Technology Austria), Prof. Nico Sommerdijk (Radboud University Medical Center, Nijmegen, the Netherlands) and Dr Dimitra Micha (Amsterdam University Medical Center, Vrije Universiteit, the Netherlands).