Vertebrate Tissues Research Articles

Diet-Host-Microbiota Interactions Shape Aryl Hydrocarbon Receptor Ligand Production to Modulate Intestinal Homeostasis.

The aryl hydrocarbon receptor (AhR) is a ligand-activated basic-helix-loop-helix transcription factor that binds structurally diverse ligands and senses cues from environmental toxicants and physiologically relevant dietary/microbiota-derived ligands. The AhR is an ancient conserved protein and is widely expressed across different tissues in vertebrates and invertebrates. AhR signaling mediates a wide range of cellular functions in a ligand-, cell type-, species-, and context-specific manner. Dysregulation of AhR signaling is linked to many developmental defects and chronic diseases. In this review, we discuss the emerging role of AhR signaling in mediating bidirectional host-microbiome interactions. We also consider evidence showing the potential for the dietary/microbial enhancement ofhealth-promoting AhR ligands to improve clinical pathway management in the context of inflammatory bowel diseases and colon tumorigenesis.

Nr0b1 (DAX1) loss of function in zebrafish causes hypothalamic defects via abnormal progenitor proliferation and differentiation

The nuclear receptor DAX-1, encoded by the NR0B1 gene, is presented in the hypothalamic tissues in humans and other vertebrates. Human patients with NR0B1 mutations often have hypothalamic-pituitary defects, but the involvement of NR0B1 in hypothalamic development and function is not well understood. Here, we report the disruption of the nr0b1 gene in zebrafish causes abnormal expression of gonadotropins, a reduction in fertilization rate, and an increase in postfasting food intake, which are indicators of abnormal hypothalamic functions. We find that loss of nr0b1 increases the number of prodynorphin (pdyn)-expressing neurons but decreases the number of pro-opiomelanocortin (pomcb)-expressing neurons in the zebrafish hypothalamic arcuate region (ARC). Further examination reveals that the proliferation of progenitor cells is reduced in the hypothalamus of nr0b1 mutant embryos accompanying the decreased expression of genes in the Notch signaling pathway. Additionally, the inhibition of Notch signaling in wild-type embryos increases the number of pdyn neurons, mimicking the nr0b1 mutant phenotype. In contrast, ectopic activation of Notch signaling in nr0b1 mutant embryos decreases the number of pdyn neurons. Taken together, our results suggest that nr0b1 regulates neural progenitor proliferation and maintenance to ensure normal hypothalamic neuron development.

Nuclear preservation in the cartilage of the Jehol dinosaur Caudipteryx

Previous findings on dinosaur cartilage material from the Late Cretaceous of Montana suggested that cartilage is a vertebrate tissue with unique characteristics that favor nuclear preservation. Here, we analyze additional dinosaur cartilage in Caudipteryx (STM4-3) from the Early Cretaceous Jehol biota of Northeast China. The cartilage fragment is highly diagenetically altered when observed in ground-sections but shows exquisite preservation after demineralization. It reveals transparent, alumino-silicified chondrocytes and brown, ironized chondrocytes. The histochemical stain Hematoxylin and Eosin (that stains the nucleus and cytoplasm in extant cells) was applied to both the demineralized cartilage of Caudipteryx and that of a chicken. The two specimens reacted identically, and one dinosaur chondrocyte revealed a nucleus with fossilized threads of chromatin. This is the second example of fossilized chromatin threads in a vertebrate material. These data show that some of the original nuclear biochemistry is preserved in this dinosaur cartilage material and further support the hypothesis that cartilage is very prone to nuclear fossilization and a perfect candidate to further understand DNA preservation in deep time.

Effect of different doses of the catecholamine epinephrine on antioxidant responses of larvae of the flesh fly Sarcophaga dux.

The production and use of pharmaceutical products have increased over the past decades, and several are considered potential or proved hazardous wastes. When contaminating the environment, they can severely impact biodiversity. The catecholamine epinephrine (adrenaline) is no exception. Epinephrine can be administered as growth promoter in cattle, and is used for anaphylaxis treatment in human. While a range of studies has examined the effects of this catecholamine on vertebrate tissues, and evidenced that it can disrupt the oxidative stress status, the effects epinephrine could have on insects have remained poorly considered. Here, we examined the physiological effects of different concentrations (0, 25, 50, and 100 μg/mL) of epinephrine on larvae of the flesh fly Sarcophaga dux. Following experimental treatments, levels of H2O2, GSH, CAT, GPx, and CEH were measured from the fat body, cuticle, gut, and hemolymph of 3rd instars. Significant differences are reported for these physiological endpoints among the considered body compartments, and epinephrine concentrations. Epinephrine treatments did not increase reactive oxygen species production (H2O2 amounts), except for gut tissues. Increased levels of GSH suggest that epinephrine may have enhanced glucose metabolism and flux towards the pentose phosphate pathway, while reducing glutamine oxidation. CAT activity was slightly increased when the concentration of epinephrine was higher. The decreased GPx activity in the fat body was consistent with GSH variations. In sum, the injection of epinephrine seemed to elicit the antioxidant response in S. dux larvae, in turn attenuating ROS production.

Host Related Risk Factors of Bovine Trypanosomosis and Vector Density in Halu District of Ilubabor Zone, West Ethiopia

Background Trypanosomosis is disease caused by unicellular parasites, trypanosome, found blood and other tissue of vertebrates; including livestock, wild life and people. It is a serious disease in domestic livestock causing a significant negative impact on food production and economic growth in many parts of the world, particularly in sub-Saharan Africa. Its epidemiology and impact on livestock production are largely determined by the prevalence and distribution of the disease and its vectors in the affected area. Aim To assess the host related risk factors of bovine trypanosomosis and apparent density of tsetse flies in four peasant associations of the study area. In relation to the host risk factors, the prevalence of bovine trypanosomosis was highest in those animals with poor body condition. Results The overall 5.32% prevalence of bovine trypanosomosis was recorded from 432 blood sample collected from randomly selected animals using Buffy coat method. Trypanosoma congolense was the dominant species 14 (60.87%). However, it was not statistically significant between sex of animals (p>0.05). The mean packed cell volume (PCV) value of the infected animals was lower (20.65%±2.85) compared to non-infected animals (25.74%±4.80). There was statistically significant difference (p<0.05) in the PCV values of infected and non-infected animals. Moreover, animals with different body condition exhibited statistically significant variation (p<0.05) in the prevalence of trypanosomosis. Overall an apparent density of the flies was 2.42 f/t/d by using mono-pyramidal and biconical traps. It indicated that, G. morsitance submorsitance, G. pallidipes and G. tachinoides were tsetse flies species caught. Conclusion Finally, this work showed that trypanosomosis is an important disease affecting the health and productivity of cattle in the district. Hence, due attention should be given to this sector so as to improve livestock production and agricultural development in the area.

Discovering a New Metabolic Pathway. Early Work with My Friend, Viswanathan Natarajan.

This article summarizes our early work with Viswanathan Natarajan in the 1980s at the University of Minnesota's Hormel Institute, when he was at the beginning of his brilliant academic career. At that time most metabolic pathways for the biosynthesis and degradation of phospholipids were well established and known in considerable detail. Hence, it was exciting to discover a novel sequence of biochemical reactions, first in dog heart and later in various other vertebrate cells and tissues that became known as the transacylation-phosphodiesterase pathway of phospholipid metabolism. Because one of the metabolites, N-arachidonoylethanolamine, produced by this reaction sequence, was later found to bind to and activate cannabinoid receptors, investigations of this pathway became part of the rapidly growing field of endocannabinoid research. This is briefly summarized here as well.

Ptk7 Is Dynamically Localized at Neural Crest Cell–Cell Contact Sites and Functions in Contact Inhibition of Locomotion

Neural crest (NC) cells are highly migratory cells that contribute to various vertebrate tissues, and whose migratory behaviors resemble cancer cell migration and invasion. Information exchange via dynamic NC cell–cell contact is one mechanism by which the directionality of migrating NC cells is controlled. One transmembrane protein that is most likely involved in this process is protein tyrosine kinase 7 (PTK7), an evolutionary conserved Wnt co-receptor that is expressed in cranial NC cells and several tumor cells. In Xenopus, Ptk7 is required for NC migration. In this study, we show that the Ptk7 protein is dynamically localized at cell–cell contact zones of migrating Xenopus NC cells and required for contact inhibition of locomotion (CIL). Using deletion constructs of Ptk7, we determined that the extracellular immunoglobulin domains of Ptk7 are important for its transient accumulation and that they mediate homophilic binding. Conversely, we found that ectopic expression of Ptk7 in non-NC cells was able to prevent NC cell invasion. However, deletion of the extracellular domains of Ptk7 abolished this effect. Thus, Ptk7 is sufficient at protecting non-NC tissue from NC cell invasion, suggesting a common role of PTK7 in contact inhibition, cell invasion, and tissue integrity.

Desmosomal Cadherins in Health and Disease.

Desmosomal cadherins are a recent evolutionary innovation that make up the adhesive core of highly specialized intercellular junctions called desmosomes. Desmosomal cadherins, which are grouped into desmogleins and desmocollins, are related to the classical cadherins, but their cytoplasmic domains are tailored for anchoring intermediate filaments instead of actin to sites of cell-cell adhesion. The resulting junctions are critical for resisting mechanical stress in tissues such as the skin and heart. Desmosomal cadherins also act as signaling hubs that promote differentiation and facilitate morphogenesis, creating more complex and effective tissue barriers in vertebrate tissues. Interference with desmosomal cadherin adhesive and supra-adhesive functions leads to a variety of autoimmune, hereditary, toxin-mediated, and malignant diseases. We review our current understanding of how desmosomal cadherins contribute to human health and disease, highlight gaps in our knowledge about their regulation and function, and introduce promising new directions toward combatting desmosome-related diseases.

Vulvo-vaginal myiasis among rural women in West Bengal, India

Myiasis, the infestation of living or dead tissue of vertebrates by larvae (maggots) of dipterous flies, is well-known in the medical field. Different parts of the human body, such as skin, oral, nasal, urogenital are affected and named accordingly. The present study was a clinic-entomological study where the women having vulvo-vaginal myiasis were included. Maggots were collected, cultured, and adult flies were identified. A total of 34 cases of vulvo-vaginal myiasis were treated. The larvae of 29 cases were cultured into adults. Most of the women are rural (94%), illiterate and from a low socioeconomic society. The authors specified the infested sites of vulva and vagina such as vaginal, labia, clitoris, episiotomy wound, vulval growth, and prolapsed uterus. The episiotomy wound (32%) is the most common infestation site, followed by the vagina (26%). Chrysomya bezziana (76%) and Chrysomya megacephala (24%) are the identified flies. Illiterate, rural puerperal mothers of low socioeconomic status without proper health education and basic hygiene knowledge are vulnerable to myiasis.

SEM Analyses of Fossilized Chondrocytes in the Extinct Birds Yanornis and Confuciusornis: Insights on Taphonomy and Modes of Preservation in the Jehol Biota

Calcified cartilage is a vertebrate tissue that has unique characteristics, such as a high percentage of calcification, avascularity and cells with apparently delayed autolytic processes after death. All of these factors suggest that fossilized cartilage may be favorable to exceptional cellular preservation, but little is known about chondrocyte fossilization overall in vertebrate paleontology. To further understand the spectrum of cellular preservation in this tissue, we analyze the morphology and the chemistry of some intralacunar content seen in previously published avian cartilage from the Early Cretaceous Jehol biota (in Yanornis and Confuciusornis). For this, we combine standard paleohistology with Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). To better identify some fossilized structures, we compare them with experimentally decayed and biofilm-invaded avian cartilage. Histological images of the cartilage of Yanornis show structures that resemble cell nuclei within chondrocyte lacunae. An SEM analysis on this cartilage shows that some lacunae are filled with a type of in vivo mineralization (similar to micropetrotic lacunae) and others are filled with small and spherical silicified cells surrounded by an amorphous carbonaceous material. These silicified cells apparently underwent postmortem cell shrinkage and do not constitute cell nuclei. Confuciusornis shows filamentous, non-spherical cells that are mostly made of silicon and carbon. This cell morphology does not resemble that of typical healthy chondrocytes, but based on comparison with decaying, biofilm-infiltrated chondrocyte lacunae from extant material, the most plausible conclusion is that the cells of Confuciusornis were partially autolyzed prior to their mineralization. In Yanornis and Confuciusornis respectively, silicification and alumino-silicification were responsible for chondrocyte preservation; while alumino-silicification and ironization occurred in their soft tissues. This shows that alumino-silicification is quite a common mechanism of cellular and soft-tissue preservation in the Jehol biota. Moreover, the two different chondrocyte morphologies (spherical and filamentous) apparently reflect two taphonomical histories, including different timings of postmortem permineralization (one rapid and one much more delayed). This type of analysis paired with more actuotaphonomy experiments will be needed in the future to better understand the preservation potential of chondrocytes and other cell types in the fossil record.

In Vivo Imaging of Newt Lens Regeneration: Novel Insights Into the Regeneration Process.

PurposeTo establish optical coherence tomography (OCT) as an in vivo imaging modality for investigating the process of newt lens regeneration.MethodsSpectral-domain OCT was employed for in vivo imaging of the newt lens regeneration process. A total of 37 newts were lentectomized and followed by OCT imaging over the course of 60 to 80 days. Histological images were obtained at several time points to compare with the corresponding OCT images. Volume measurements were also acquired.ResultsOCT can identify the key features observed in corresponding histological images based on the scattering differences from various eye tissues, such as the cornea, intact and regenerated lens, and the iris. Lens volume measurements from three-dimensional OCT images showed that the regenerating lens size increased linearly until 60 days post-lentectomy.ConclusionsUsing OCT imaging, we were able to track the entire process of newt lens regeneration in vivo for the first time. Three-dimensional OCT images allowed us to volumetrically quantify and visualize the dynamic spatial relationships between tissues during the regeneration process. Our results establish OCT as an in vivo imaging modality to track/analyze the entire lens regeneration process from the same animal.Translational RelevanceLens regeneration in newts represents a unique example of vertebrate tissue plasticity. Investigating the cellular and morphological events that govern this extraordinary process in vivo will advance our understanding and shed light on developing new therapies to treat blinding disorders in higher vertebrates.

Optimizing imaging depth of anisotropic scattering tissues with polarization engineered second harmonic generation microscopy

Connective tissues in vertebrates consist of many anisotropic structures formed by collagen and muscle fibers, which could also generate intense second harmonic (SH). In SHG based tissue imaging, the incident light, when subjected to birefringence and scattering, would lead to a rapid decrement in imaging depth. The work simulating polarized light propagating through a thick and highly-scattering semi-infinite medium using a polarization-sensitive Monte Carlo model find that circular polarization would achieve deeper penetration depth. Henceforth, we use polarization engineered SHG imaging to investigate fish scales and pig tendon/dermis of various thickness, as well as the corresponding depolarization effect as a function of the imaging depth in this work. Critically, we have verified quantitatively the previous simulation results and presented the possibility to greatly improve the imaging of thick anisotropic and scattering tissues through engineering polarization. In parallel to wavefront shaping that uses a spatial light modulator or a wavefront sensor based deformable mirror to increase the signal-to-background (SBR) ratio in imaging, our approach is simple, effective, and sensitive to tissue anisotropy.

Chiral HPLC separation of enantiomeric blebbistatin derivatives and racemization analysis in vertebrate tissues

Simple and consistent chiral HPLC methods for the efficient separation of enantiomeric blebbistatin derivatives, namely parent compound blebbistatin and derivatives 4-nitroblebbistatin, 4-aminoblebbistatin, 4-dimethylaminoblebbistatin, and 4-t-butylblebbistatin were developed using cellulose tris(3,5-dimethylphenylcarbamate) as a stationary phase (Lux cellulose-1 column). Blebbistatin, 4-aminoblebbistatin, and 4-dimethylaminoblebbistatin racemates were well-separated in normal-phase HPLC conditions while 4-nitroblebbistatin and 4-t-butylblebbistatin were effectively separated in both normal- and reversed-phase HPLC conditions. Furthermore, the order of elution of enantiopure compounds was found to be independent of mobile phase compositions and conditions used, and solely depends on the interaction between the enantiomer and the chiral stationary phase. We found that despite the chiral center being present far from the D-ring in the blebbistatin structure, the D-ring substitutions prominently affect the chiral separation. Ex vivo racemization studies of the most popular blebbistatin derivative (S)-(–)-4-aminoblebbistatin in rat blood and brain tissues revealed that the compound does not convert into the inactive enantiomer. This confirms that (S)-(–)-4-aminoblebbistatin is a useful tool compound in cellular and molecular biology studies without the risks of racemization and degradation effects.

Targeting of SET/I2PP2A oncoprotein inhibits Gli1 transcription revealing a new modulator of Hedgehog signaling

The Hedgehog (Hh)/Gli signaling pathway controls cell proliferation and differentiation, is critical for the development of nearly every tissue and organ in vertebrates and is also involved in tumorigenesis. In this study, we characterize the oncoprotein SET/I2PP2A as a novel regulator of Hh signaling. Our previous work has shown that the zebrafish homologs of SET are expressed during early development and localized in the ciliated organs. In the present work, we show that CRISPR/Cas9-mediated knockdown of setb gene in zebrafish embryos resulted in cyclopia, a characteristic patterning defect previously reported in Hh mutants. Consistent with these findings, targeting setb gene using CRISPR/Cas9 or a setb morpholino, reduced Gli1-dependent mCherry expression in the Hedgehog reporter zebrafish line Tg(12xGliBS:mCherry-NLS). Likewise, SET loss of function by means of pharmacological inhibition and gene knockdown prevented the increase of Gli1 expression in mammalian cells in vitro. Conversely, overexpression of SET resulted in an increase of the expression of a Gli-dependent luciferase reporter, an effect likely attributable to the relief of the Sufu-mediated inhibition of Gli1. Collectively, our data support the involvement of SET in Gli1-mediated transcription and suggest the oncoprotein SET/I2PP2A as a new modulator of Hedgehog signaling.

Molecular genetic determinants for the development of dental caries

Various factors, both internal and external, lead to the development of caries. Today, the study of molecular genetic predictors of disease, including dental caries, has become widespread. We searched for literature sources in domestic and foreign scientometric databases in order to study the current state of the molecular genetic mechanisms of dental caries. Studies of the inheritance of dental caries in children using the twin method have clearly shown the key role of genetic markers in the development of the disease. Predisposition or resistance to caries may be the result of one or more genotypes, phenotypes and environmental influences. Tooth enamel is one of the most mineralized tissues in vertebrates, which is characterized by high strength and high compactness. Enamel formation is the result of a series of ectomesenchymal interactions. Enamel defects occur as a result of disturbances in the formation of teeth and can lead to changes in the formation of enamel or calcification of the organic matrix. Particular attention should be paid to enamel defects that occur as a result of disorders in the formation of teeth and can lead to changes in the formation of enamel or calcification of the organic matrix. Insufficiently mineralized or irregular enamel structure can lead to caries. Differential genetic factors on different anatomical structures of teeth, different surfaces of deciduous and permanent teeth also contribute to the development of carious lesions. In addition to defective mineralization, genotypic variations also make enamel more vulnerable. Numerous studies have established the role of inheritance of dental caries and identified the main genes that ensure the resistance of enamel to cariogenic factors, the completeness of the composition of saliva and the rate of salivation. Keywords: caries, molecular genetic determinants, amelogenesis genes, dentinogenesis genes.

Schwann cell precursors generate sympathoadrenal system during zebrafish development.

The autonomic portion of the peripheral nervous system orchestrates tissue homeostasis through direct innervation of internal organs, and via release of adrenalin and noradrenalin into the blood flow. The developmental mechanisms behind the formation of autonomic neurons and chromaffin cells are not fully understood. Using genetic tracing, we discovered that a significant proportion of sympathetic neurons in zebrafish originates from Schwann cell precursors (SCPs) during a defined period of embryonic development. Moreover, SCPs give rise to the main portion of the chromaffin cells, as well as to a significant proportion of enteric and other autonomic neurons associated with internal organs. The conversion of SCPs into neuronal and chromaffin cells is ErbB receptor dependent, as the pharmacological inhibition of the ErbB pathway effectively perturbed this transition. Finally, using genetic ablations, we revealed that SCPs producing neurons and chromaffin cells migrate along spinal motor axons to reach appropriate target locations. This study reveals the evolutionary conservation of SCP-to-neuron and SCP-to-chromaffin cell transitions over significant growth periods in fish and highlights relevant cellular-genetic mechanisms. Based on this, we anticipate that multipotent SCPs might be present in postnatal vertebrate tissues, retaining the capacity to regenerate autonomic neurons and chromaffin cells.

Spindle positioning and its impact on vertebrate tissue architecture and cell fate.

In multicellular systems, oriented cell divisions are essential for morphogenesis and homeostasis as they determine the position of daughter cells within the tissue and also, in many cases, their fate. Early studies in invertebrates led to the identification of conserved core mechanisms of mitotic spindle positioning centred on the Gαi-LGN-NuMA-dynein complex. In recent years, much has been learnt about the way this complex functions in vertebrate cells. In particular, studies addressed how the Gαi-LGN-NuMA-dynein complex dynamically crosstalks with astral microtubules and the actin cytoskeleton, and how it is regulated to orient the spindle according to cellular and tissue-wide cues. We have also begun to understand how dynein motors and actin regulators interact with mechanosensitive adhesion molecules sensing extracellular mechanical stimuli, such as cadherins and integrins, and with signalling pathways so as to respond to extracellular cues instructing the orientation of the division axis in vivo. In this Review, with the focus on epithelial tissues, we discuss the molecular mechanisms of mitotic spindle orientation in vertebrate cells, and how this machinery is regulated by epithelial cues and extracellular signals to maintain tissue cohesiveness during mitosis. We also outline recent knowledge of how spindle orientation impacts tissue architecture in epithelia and its emerging links to the regulation of cell fate decisions. Finally, we describe how defective spindle orientation can be corrected or its effects eliminated in tissues under physiological conditions, and the pathological implications associated with spindle misorientation.

14C DATES AND STABLE ISOTOPE ECOLOGY OF MARINE VERTEBRATES IN THE LATE PLEISTOCENE-EARLY HOLOCENE CHAMPLAIN SEA

ABSTRACTThe late Pleistocene to early Holocene Champlain Sea provides a unique opportunity to study the development of marine ecosystems in a context of global climatic change. This study presents radiocarbon (14C) dates and stable isotope analyses on 15 vertebrate specimens from Champlain Sea sediments, including the Charlotte Whale, which is Vermont’s State marine fossil. Data are used in an attempt to investigate the timing of colonization and ecological dynamics in this newly formed sea. Using the average marine correction,14C dates on four specimens likely calibrate prior to or possibly synchronous with the accepted origination date for the Champlain Sea, implying larger marine reservoir effects than the average marine correction in the vertebrate tissues. Without knowing the specific marine reservoir offsets, it is not possible to calculate the timing of colonization or its relation to concurrent climatic change. Observed lower δ13C and δ15N values in walruses, a fin whale, and a right whale support consumption of prey from lower trophic levels such as bivalve mollusks, krill, and copepods. Higher isotopic values in beluga whales and a bird, the thick-billed murre, support consuming fish, such as cod and capelin. These isotopic data show comparable values and relationships as observed in modern arctic marine ecosystems.

Early-Life Corticosterone Body Condition Influence Social Status and Survival in a Food-Caching Passerine.

Individuals undergo profound changes throughout their early life as they grow and transition between life-history stages. As a result, the conditions that individuals experience during development can have both immediate and lasting effects on their physiology, behavior, and, ultimately, fitness. In a population of Canada jays in Algonquin Provincial Park, Ontario, Canada, we characterized the diet composition and physiological profile of young jays at three key time points during development (nestling, pre-fledge, and pre-dispersal) by quantifying stable-carbon (δ13C) and -nitrogen (δ15N) isotopes and corticosterone concentrations in feathers. We then investigated the downstream effects of early-life diet composition, feather corticosterone, and environmental conditions on a juvenile's social status, body condition, and probability of being observed in the fall following hatch. Across the three time points, the diet of Canada jay young was composed primarily of vertebrate tissue and human food with the proportion of these food items increasing as the jays neared dispersal. Feather corticosterone concentrations also shifted across the three time points, decreasing from nestling to pre-dispersal. Dominant juveniles had elevated corticosterone concentrations in their feathers grown pre-dispersal compared with subordinates. High body condition as nestlings was associated with high body condition as juveniles and an increased probability of being observed in the fall. Together, our results demonstrate that nestling physiology and body condition influence the social status and body condition once individuals are independent, with potential long-term consequences on survival and fitness.

Mechanical Strain Alters the Surface Charge of Collagen Fibrils.

Collagen fibrils act like nanoscale cables in the extracellular matrix of vertebrate tissues and provide a scaffold for cells to attach to. However, beyond this mechanical function, the surface charge of collagen fibrils is also likely to play an important role. Here, we show that native, type I collagen fibrils from a mammal tendon exhibit a particular dependence of surface charge on longitudinal strain. Fibrils first become more positive with strain of up to 10% and then become more negative again with strain between 10 and 17%. The effect correlates with the stiffness of fibrils and can be explained by structural rearrangements, which expose hidden, ionizable residues. Fibrils treated with glutaraldehyde did not show any change in surface charge when strained. The electrical surface potential, which is directly related to the number ratio of exposed amine and carboxy groups on the surface, was determined by Kelvin-probe force microscopy of fibrils attached on an extensible, thin polymer film. By stretching the film, a large number of individual fibrils could be strained simultaneously without resorting to sophisticated nanomechanical devices. It is conceivable that cells react to such changes of the fibril charge and that this effect is an additional contributor, besides mechanics, to a number of physiological processes. It may also need to be considered in the design of tissue-engineering scaffolds.