Molybdenum’s role in biology is critical due to its catalytic prowess. It facilitates essential enzymatic reactions that enhance the speed and efficiency of biochemical processes like nitrogen fixation—a cornerstone for constructing life’s building blocks. Without this metal, these reactions could still proceed but at rates too sluggish to support life’s complex biosphere. Thus, molybdenum acts as a biochemical accelerator, enabling early organisms to flourish in otherwise inhospitable primordial conditions.

What renders this finding particularly intriguing is the paradoxical context of molybdenum’s availability. Geological data indicates that the early Earth environment contained notably low levels of free molybdenum, especially prior to the rise of oxygenic photosynthesis which dramatically altered Earth’s geochemistry. Aya Klos, a PhD candidate in bacteriology and co-author of the study, emphasizes the counterintuitive nature of this phenomenon: “Though molybdenum was scarce billions of years ago, early life nonetheless evolved complex systems reliant on it.”

The persistence of molybdenum-dependent biochemical pathways despite scarcity suggests there was a significant evolutionary advantage. It raises compelling questions about why early biochemistry favored molybdenum amidst more abundant metals. The study’s authors speculate that molybdenum’s unique chemical properties—such as its redox flexibility and ability to stabilize complex enzyme structures—may have outweighed the benefits of more plentiful alternatives.

To disentangle these evolutionary choices, the researchers meticulously tracked molybdenum’s intracellular movements. Their investigations extended beyond mere presence, focusing on how cells transported and utilized molybdenum at the molecular level. These intricate mechanisms demonstrate an early biological investment in acquiring and harnessing molybdenum with high specificity, pointing to a deep evolutionary origin of intricate metal transport and homeostasis systems.

Intriguingly, alongside molybdenum, the team also traced the ancient biological use of tungsten, another transition metal with catalytic abilities analogous to molybdenum but generally associated with extremophile organisms today. This dual detection implies that early life was not only experimenting with molybdenum but was simultaneously exploring alternative metal cofactors like tungsten to optimize biochemical pathways under early Earth conditions.

Betül Kaçar, the senior author and bacteriology professor at UW–Madison, notes that understanding which elements underpinned early life offers critical insights for the field of astrobiology. By knowing which metals life depended on billions of years ago, scientists can better predict what chemical signatures to search for on other planets when investigating their potential habitability and the presence of life.

This discovery challenges traditional assumptions about early Earth biochemistry. It highlights that scarcity of an element in the environment does not necessarily preclude its adoption by evolving life. Instead, the biochemical utility and adaptability of life drive selective incorporation of elements, even when rare. “Life works in surprising ways,” Kaçar reflects. “Our findings compel us to expand our imaginative scope when searching for life beyond Earth.”

The implications of this study extend beyond pure evolutionary biology. They reach into geochemistry, molecular biology, and the search for extraterrestrial life. The detailed molecular investigation of ancient metal utilization provides a template for understanding how biological complexity emerged in metal-poor worlds and how life might adapt to unfamiliar planetary chemistries.

Support for this research was robust, mobilizing resources from the NASA Interdisciplinary Consortium for Astrobiology Research, NASA Astrobiology Program Grants, and the Natural Environment Research Council. Additional fellowships and postdoctoral programs strengthened the team’s capacity to employ advanced data and statistical analyses necessary for reconstructing ancient biochemical histories.

By synthesizing geological records with cellular biochemistry data, this study exemplifies modern interdisciplinary science. Such integrative approaches are essential for deconvoluting early life’s molecular evolution and framing planetary habitability questions in relevant chemical and biological contexts.

In the grand narrative of Earth’s history, the incorporation of molybdenum and tungsten into life’s molecular architecture tells a compelling story of resourcefulness and adaptability. It demonstrates how life’s molecular machinery can pioneer novel solutions, transcending environmental limitations to carve out environments conducive to prolonged evolution and diversification.

This research redefines our understanding of early biochemical landscapes and paves the way for new paradigms in evolutionary science and astrobiology. It urges scientists to reconsider which chemical elements should be regarded as critical biosignatures and emphasizes the value of studying trace elements in ancient and modern biological systems alike.

Subject of Research: Not applicable

Article Title: Biological use of molybdenum and tungsten stems back to 3.4 billion years ago

News Publication Date: 5-May-2026

Web References: http://dx.doi.org/10.1038/s41467-026-72133-0

References: https://doi.org/10.1038/s41467-026-72133-0

Keywords: molybdenum, tungsten, early Earth, biochemical evolution, nitrogen fixation, astrobiology, metal utilization, enzymatic catalysis, ancient life, geochemistry

At its core, cell movement has always been modeled assuming positive viscosity—a drag force that inherently resists motion, akin to pushing through a fluid like honey or oil. Viscosity, a measure of a substance’s resistance to flow or deformation, generally acts as a dissipative factor slowing motion. For decades, scientists accepted that within cellular assemblies, this viscosity would impede the ability of cells to migrate collectively, particularly in tightly packed epithelial layers essential for forming barriers and repairing tissue. However, the latest research led by Associate Professor Jacob Notbohm and PhD candidate Molly McCord has turned this assumption on its head by demonstrating that, in certain conditions, cellular collectives generate negative viscosity.

The team’s pioneering methodology involved an innovative combination of optical imaging and mechanical analysis. By observing how monocultures of epithelial cells deformed an underlying compliant gel substrate as they migrated, they were able to quantify the forces these cells exerted on their environment with unprecedented spatial resolution. Beyond just cataloging force magnitudes, McCord developed an advanced analytical framework to dissect viscosity values not only at the cellular level but across multicellular regions within the monolayer. Unexpectedly, areas emerged where viscosity values dipped below zero—a hallmark of negative viscosity suggesting that instead of resisting motion, these cells actively contributed energy to propel collective movement.

To conceptualize this phenomenon, Notbohm draws an analogy to driving a car: “Imagine a vehicle moving through air, which normally provides drag, slowing it down. Negative viscosity would be like the air instead pushing the car forward, adding energy rather than removing it.” While initially counterintuitive and seemingly contradictory to foundational physical laws, negative viscosity is permissible in active biological systems that continuously transduce chemical energy into mechanical work. The cells, powered by metabolic processes converting nutrients into usable energy, can therefore exhibit complex mechanical behaviors not seen in passive materials.

Delving deeper, the researchers correlated regions of negative viscosity with heightened metabolic activity, underscoring the biological underpinnings of this mechanical anomaly. Cells in these zones exhibited elevated energy consumption, reflecting a biochemical state primed to generate motion-enhancing forces within the cellular collective. This discovery elegantly links cellular energetics with emergent mechanical properties, suggesting a coordinated interplay where bioenergetics directly modulates the physical characteristics of tissue motion. Such insights provide a fresh framework to reevaluate how cellular systems integrate metabolic cues with mechanical outputs.

The ramifications of uncovering negative viscosity stretch beyond basic science, offering transformative possibilities for medical and bioengineering disciplines. Wound healing, an inherently collective cellular process requiring coordinated migration to restore tissue integrity, may be influenced by modulating these viscous properties. Accelerating or directing collective movement by harnessing or mimicking negative viscosity mechanisms could pave the way for therapies that improve recovery outcomes and reduce chronic wound complications.

Similarly, the findings may illuminate key processes in embryonic development and tissue morphogenesis, where precise cell group movements sculpt form and function. Understanding the mechanical language of cells operating under negative viscosity could unravel developmental pathologies and offer avenues to engineer tissues with enhanced regenerative capabilities. By integrating these mechanical principles into computational models, researchers can predict and potentially control how cells behave within complex multicellular systems.

Furthermore, the study breaks ground on quantifying a parameter that had eluded direct measurement—effective viscosity within cell monolayers. Prior attempts to model collective cell motion often lacked empirical measures of viscous resistance, limiting predictive accuracy. McCord and Notbohm’s experimental approach fills this critical gap, providing a robust platform for future investigations on cellular mechanics. This quantitative advance enables refinement of biophysical models, enhancing understanding of force generation, tissue rheology, and mechanotransduction.

The implications of negative viscosity extend to the realm of active matter physics, where biological systems are viewed through the lens of nonequilibrium thermodynamics. Cells, as active materials, convert stored energy into mechanical work, displaying properties unattainable in inanimate matter at equilibrium. Demonstrating negative viscosity in epithelial monolayers not only supports active matter theories but encourages cross-disciplinary dialogues bridging biology, physics, and engineering.

While the discovery is compelling, the research community acknowledges that much remains to be explored. How widespread is negative viscosity among different cell types and tissues? What molecular mechanisms govern the transition from positive to negative viscosity states? Can external factors such as biochemical signals or mechanical constraints modulate this property? Addressing these questions will deepen mechanistic insights and unlock new frontiers in cellular biomechanics.

The research, funded by the National Science Foundation and the National Institutes of Health, exemplifies how interdisciplinary collaboration enhances innovation. By combining experimental mechanics, advanced imaging, and biological analysis, the team achieved a synthesis of quantitative rigor and physiological relevance that sets new standards in the field.

In conclusion, the identification of negative viscosity within epithelial cell collectives marks a paradigm shift in our comprehension of cellular motion. It challenges prevailing assumptions and opens avenues that span from fundamental science to applied medicine. As this novel concept gains momentum, it promises to reshape the landscape of cellular biomechanics and inspire inventive strategies to manipulate tissue dynamics for health and disease.

Subject of Research: Cells

Article Title: Energy Injection in an Epithelial Cell Monolayer Indicated by Negative Viscosity

News Publication Date: 4-Dec-2025

Web References: https://journals.aps.org/prxlife/abstract/10.1103/9lnm-gm3j

References: Not specified beyond the journal article.

Image Credits: Joel Hallberg / UW–Madison

Keywords

Cells, Cell Biology, Biomechanics, Negative Viscosity, Epithelial Cells, Collective Cell Migration, Active Matter, Tissue Mechanics, Wound Healing, Cell Metabolism, Biophysics, Tissue Development

Telomeres serve as a biological clock for cells, protecting chromosome ends from deterioration and preventing unwanted fusion with neighboring chromosomes. These repetitive DNA sequences and their associated proteins gradually shorten with age, a process tightly linked to cellular aging and death. However, when telomere maintenance falters prematurely, it results in genomic instability that can precipitate conditions such as cancer, bone marrow failure syndromes, and other degenerative diseases. The enzyme telomerase has the unique ability to extend these sequences, but the mechanisms governing its activity in human cells remain incompletely understood.

The research team, led by Professor Ci Ji Lim of the UW–Madison biochemistry department, employed cutting-edge computational biology tools to probe these mechanisms. Leveraging AlphaFold, a sophisticated machine learning platform designed to predict protein structures and interactions with remarkable accuracy, the team sought to discover novel proteins that interface with human telomerase. This computational prediction yielded a surprising candidate: human replication protein A (RPA), a protein complex historically characterized as a key player in DNA replication and repair pathways but not previously confirmed to have a direct impact on telomerase activity.

RPA is known to bind single-stranded DNA during replication and maintain genome integrity by stabilizing DNA structures and recruiting repair proteins. The current study postulated that RPA’s ability to interact with telomerase could be fundamental to sustaining telomere length in human cells. Guided by the AlphaFold predictions, experimental assays were conducted to verify the physical and functional interactions between RPA and the telomerase enzyme complex. The results unequivocally demonstrated that RPA is indispensable for the processivity of telomerase, effectively enabling telomerase to elongate telomeres efficiently.

Perhaps most significantly, the region where RPA docks onto the telomerase complex correlates precisely with structural variants of telomerase found in patients suffering from disorders that include aplastic anemia, myelodysplastic syndrome, and acute myeloid leukemia. These diseases, often linked to critically shortened telomeres, have perplexed clinicians due to the absence of identifiable mutations in the telomerase subunits themselves. The team’s findings suggest that mutations interfering with the interaction between RPA and telomerase could be the unseen culprits behind these clinical presentations.

The clinical implications of this research are immediate and profound. For years, there have been patients with shortened telomere syndromes without a clear genetic diagnosis, impeding targeted treatment strategies. Now, mutations disrupting RPA’s telomerase-stimulating function provide a molecular explanation for some of these enigmatic cases. Testing for mutations in RPA or its interaction interfaces could become a new standard in genetic panels for diagnosing telomere biology disorders, thus facilitating precision medicine tailored to the underlying molecular defects.

Moreover, the study underscores the broader potential of integrating artificial intelligence-driven structural predictions with biochemical validation to uncover hidden layers of cellular regulation. As lab-based experiments confirmed AlphaFold’s computational insights, this synergistic approach may accelerate the discovery of other critical protein interactions involved in genome maintenance and disease pathology. This integration of AI and bench science heralds a new era in molecular biology research, where in silico models guide high-impact discovery pipelines.

Over 12 months following their publication, Lim and his colleagues have received an influx of inquiries from international clinicians and scientists eager to investigate whether their patients’ unresolved telomere disorders can be traced to compromised RPA-telomerase interactions. The global response attests to the urgent demand for novel diagnostic markers and mechanistic understanding in telomere biology diseases, emphasizing the transformative nature of this research for patients and families.

Beyond its direct clinical relevance, the study expands the fundamental biological understanding of telomere maintenance. It places RPA at the heart of telomerase regulation, linking two essential arms of DNA metabolism: replication and telomere elongation. This finding invites further exploration of how disruptions in these tightly coordinated processes contribute to genomic instability, aging, and malignant transformation, potentially revealing new targets for therapeutic intervention.

The work, supported by the National Institutes of Health and multiple UW–Madison research centers, represents a multidisciplinary collaboration encompassing molecular biochemistry, chemistry, structural biology, and computational modeling. Such collaborative efforts exemplify the integrative approach required to tackle complex biological questions and translate them into meaningful clinical advances.

Lastly, this discovery paves the way for future research into how other known DNA repair and replication proteins might influence telomerase function. It raises fundamental questions about the network of protein interactions that safeguard chromosome ends and the molecular basis by which their dysfunction leads to disease. As scientists dissect these intricate relationships, new strategies to manipulate telomerase activity therapeutically may emerge, offering hope for patients afflicted with telomere-related disorders.

Subject of Research: The critical role of human Replication Protein A (RPA) as a telomerase processivity factor in telomere maintenance and its implications in telomere-related diseases.

Article Title: Human RPA is an essential telomerase processivity factor for maintaining telomeres

News Publication Date: 30-Oct-2025

Web References: https://doi.org/10.1126/science.ads5297

Image Credits: Ci Ji Lim

Keywords: telomerase, telomeres, replication protein A, RPA, DNA repair, chromosome stability, telomere maintenance, telomere diseases, aplastic anemia, myelodysplastic syndrome, acute myeloid leukemia, AlphaFold, protein-protein interaction, genome integrity, molecular biology, chromosome aging