Biology subjects

Merino, C.

Publications and source records attributed to Merino, C..

3 recordsLinked to original sources

bioRxiv2025

Shape, Strain, and Stability: Epithelia Under High Strain

Mechanical forces play crucial roles in epithelia tissue morphogenesis and function, yet individual cells often respond differently to the same external force. Strain heterogeneity, the non-uniform deformation of cells under uniform external mechanical stimuli, may underlie tissue-level robustness and guide morphogenetic outcomes. In this study, we applied a defined uniaxial strain to Xenopus laevis epithelial explants and investigated how strain was distributed at the cellular level. Live imaging and quantitative analysis revealed that despite a uniform tissue-level strain, cellular strain was heterogeneous, suggesting variable responses to a uniform mechanical stimulus. To understand the source of this variability, we used an image analysis pipeline to explore multiple aspects of cell morphology. We found that cell intrinsic material properties, represented by Poisson index, had the strongest correlation with strain heterogeneity, suggesting a dominant role in variable mechanical response. We further analyzed how force was distributed at the cellular level using a vinculin force sensor and laser ablation. These experiments demonstrated that forces are primarily transmitted through the medio-apical actomyosin cortex whereas junctional actomyosin facilitates dissipation and remodeling. These findings provide new insights into the physical principles that underlie epithelial resilience and adaptive remodeling, highlighting the importance of distinct functions of junctional and medio-apical actomyosin networks in mechanical adaptation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/687918v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1d27474org.highwire.dtl.DTLVardef@1db811forg.highwire.dtl.DTLVardef@1fa36dforg.highwire.dtl.DTLVardef@288107_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Remodelling of Skeletal Muscle Myosin Metabolic States in Hibernating Mammals

Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, Ictidomys tridecemlineatus and Eliomys quercinus and larger hibernators, Ursus arctos and Ursus americanus. We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure in U. arctos and U. americanus during hibernation, whilst in I. tridecemlineatus and E. quercinus, changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20{degrees}C). Upon repeating loaded Mant-ATP chase experiments at 8{degrees}C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77-107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor in I. tridecemilineatus, which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.

physiology↗

bioRxiv2021

Toxicity of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) in early development: a wide-scope metabolomics assay in zebrafish embryos

The tobacco-specific nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic and ubiquitous environmental pollutant which carcinogenic and cytotoxic activity has been thoroughly investigated in murine models and human tissues. However, its potential deleterious effects on vertebrate early development are yet poorly understood. In this work, we characterized the impact of NNK exposure during early developmental stages of zebrafish embryos, a known alternative model for mammalian toxicity studies. Embryos exposed to different NNK concentrations were monitored for lethality and for the appearance of malformations during the first five days after fertilization. LC/MS-based untargeted metabolomics was subsequently performed for a wide-scope assay of NNK-related metabolic alterations. Our results revealed the presence of not only the parental compound, but also of two NKK known metabolites, 4-Hydroxy-4-(3-pyridyl)-butyric acid (HPBA) and 4-(Methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol (NNAL-N-oxide) in exposed embryos likely resulting from active CYP450-mediated -hydroxylation and NNK detoxification pathways, respectively. This was paralleled by a disruption in purine and pyrimidine metabolisms and the activation of the base excision repair pathway. Our results confirm NNK as a harmful embryonic agent and demonstrate zebrafish embryos to be a suitable early development model to monitor NNK toxicity.

pharmacology and toxicology↗