scholarly journals Protein Charge Neutralization is the Proximate Driver Dynamically Tuning a Nanoscale Bragg Reflector

2021 ◽  
Author(s):  
Robert Levenson ◽  
Brandon Malady ◽  
Tyler Lee ◽  
Yahya Al Sabeh ◽  
Phillip Kohl ◽  
...  
Keyword(s):  
Osmotic Dehydration ◽  
Bragg Reflector ◽  
Fine Tuning ◽  
Lamellar Thickness ◽  
Ph Titration ◽  
Charge Neutralization ◽  
Precise Control ◽  
Skin Cells

AbstractReflectin is a cationic, block copolymeric protein that mediates the dynamic fine-tuning of color and brightness of light reflected from nanostructured Bragg reflectors in iridocyte skin cells of squids. In vivo, neuronally activated phosphorylation of reflectin triggers its assembly, driving osmotic dehydration of the membrane-bounded Bragg lamellae containing the protein to simultaneously shrink the lamellar thickness and spacing while increasing its refractive index contrast, thus tuning the wavelength and increasing the brightness of reflectance. In vitro, we show that reduction in repulsive net charge of the purified, recombinant reflectin – either (for the first time) by generalized anionic screening with salt, or by pH titration - drives a finely tuned, precisely calibrated increase in size of the resulting multimeric assemblies. The calculated effects of phosphorylation in vivo are consistent with these effects observed in vitro. X-ray scattering analyses confirm the sphericity, size and low polydispersity of the assemblies. Precise proportionality between assembly size and charge-neutralization is enabled by the demonstrated rapid dynamic arrest of multimer growth. The resulting stability of reflectin assemblies with time ensures reciprocally precise control of the particle number concentration, thereby encoding a precise calibration between the extent of neuronal signaling, osmotic pressure, and the resulting optical changes. The results presented here strongly suggest that it is charge neutralization, rather than any change in aromatic content, that is the proximate driver of assembly, fine-tuning a colligative property-based nanostructured biological machine. A physical mechanism is proposed.

scholarly journals 99mTc Labelling Strategies for the Development of Potential Nitroimidazolic Hypoxia Imaging Agents

Inorganics ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. 128 ◽  
Author(s):  
Giglio ◽  
Rey
Keyword(s):  
Rational Design ◽  
Biological Properties ◽  
Fine Tuning ◽  
Oxidation States ◽  
Hypoxia Imaging ◽  
Biological Target ◽  
99Mtc Radiopharmaceuticals ◽  
99Mtc Labelling

Technetium-99m has a rich coordination chemistry that offers many possibilities in terms of oxidation states and donor atom sets. Modifications in the structure of the technetium complexes could be very useful for fine tuning the physicochemical and biological properties of potential 99mTc radiopharmaceuticals. However, systematic study of the influence of the labelling strategy on the “in vitro” and “in vivo” behaviour is necessary for a rational design of radiopharmaceuticals. Herein we present a review of the influence of the Tc complexes’ molecular structure on the biodistribution and the interaction with the biological target of potential nitroimidazolic hypoxia imaging radiopharmaceuticals presented in the literature from 2010 to the present. Comparison with the gold standard [18F]Fluoromisonidazole (FMISO) is also presented.

scholarly journals Paracrine Secreted Frizzled-Related Protein 4 Inhibits Melanocytes Differentiation in Hair Follicle

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Haiying Guo ◽  
Mingxing Lei ◽  
Yuhong Li ◽  
Yingxin Liu ◽  
Yinhong Tang ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Hair Follicle ◽  
Skin Pigmentation ◽  
Related Protein ◽  
Skin Cells ◽  
Melanocyte Stem Cells ◽  
Potential Therapeutic Application ◽  
Pigmentation Disorders

Wnt signaling plays crucial role in regulating melanocyte stem cells/melanocyte differentiation in the hair follicle. However, how the Wnt signaling is balanced to be overactivated to control follicular melanocytes behavior remains unknown. Here, by using immunofluorescence staining, we showed that secreted frizzled-related protein 4 (sFRP4) is preferentially expressed in the skin epidermal cells rather than in melanocytes. By overexpression of sFRP4 in skin cells in vivo and in vitro, we found that sFRP4 attenuates activation of Wnt signaling, resulting in decrease of melanocytes differentiation in the regenerating hair follicle. Our findings unveiled a new regulator that involves modulating melanocytes differentiation through a paracrine mechanism in hair follicle, supplying a hope for potential therapeutic application to treat skin pigmentation disorders.

scholarly journals Modified Nanodiamonds as a Means of Polymer Surface Functionalization. From Fouling Suppression to Biosensor Design

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2980
Author(s):  
Pavel V. Melnikov ◽  
Anastasia Yu. Alexandrovskaya ◽  
Alina O. Naumova ◽  
Nadezhda M. Popova ◽  
Boris V. Spitsyn ◽  
...  
Keyword(s):  
Optical Sensors ◽  
Polymer Surface ◽  
Mixed Composition ◽  
Precise Control ◽  
Polar Groups ◽  
Bactericidal Properties ◽  
Wall Interaction ◽  
Biosensor Response

The development of different methods for tuning surface properties is currently of great interest. The presented work is devoted to the use of modified nanodiamonds to control the wetting and biological fouling of polymers using optical sensors as an example. We have shown that, depending on the type of modification and the amount of nanodiamonds, the surface of the same fluorinated polymer can have both bactericidal properties and, on the contrary, good adhesion to the biomaterial. The precise control of wetting and biofouling properties of the surface was achieved by the optimization of the modified nanodiamonds thermal anchoring conditions. In vitro and in vivo tests have shown that the fixation of amine functional groups leads to inhibition of biological activity, while the presence of a large number of polar groups of mixed composition (amide and acid chloride) promotes adhesion of the biomaterial and allows one to create a biosensor on-site. A comprehensive study made it possible to establish that in the first 5 days the observed biosensor response is provided by cells adhered to the surface due to the cell wall interaction. On the 7th day, the cells are fixed by means of the polysaccharide matrix, which provides much better retention on the surface and a noticeably greater response to substrate injections. Nevertheless, it is important to note that even 1.5 h of incubation is sufficient for the formation of the reliable bioreceptor on the surface with the modified nanodiamonds. The approach demonstrated in this work makes it possible to easily and quickly isolate the microbiome on the surface of the sensor and perform the necessary studies of its substrate specificity or resistance to toxic effects.

scholarly journals Fine-tuning of Epithelial EGFR signals Supports Coordinated Mammary Gland Development

2020 ◽  
Author(s):  
Alexandr Samocha ◽  
Hanna M. Doh ◽  
Vaishnavi Sitarama ◽  
Quy H. Nguyen ◽  
Oghenekevwe Gbenedio ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelium ◽  
Gene Signature ◽  
Mammary Epithelial ◽  
Fine Tuning ◽  
Basal Cells ◽  
Stem And Progenitor Cells

SummaryDuring puberty, robust morphogenesis occurs in the mammary gland; stem- and progenitor-cells develop into mature basal- and luminal-cells to form the ductal tree. The receptor signals that govern this process in mammary epithelial cells (MECs) are incompletely understood. The EGFR has been implicated and here we focused on EGFR’s downstream pathway component Rasgrp1. We find that Rasgrp1 dampens EGF-triggered signals in MECs. Biochemically and in vitro, Rasgrp1 perturbation results in increased EGFR-Ras-PI3K-AKT and mTORC1-S6 kinase signals, increased EGF-induced proliferation, and aberrant branching-capacity in 3D cultures. However, in vivo, Rasgrp1 perturbation results in delayed ductal tree maturation with shortened branches and reduced cellularity. Rasgrp1-deficient MEC organoids revealed lower frequencies of basal cells, the compartment that incorporates stem cells. Molecularly, EGF effectively counteracts Wnt signal-driven stem cell gene signature in organoids. Collectively, these studies demonstrate the need for fine-tuning of EGFR signals to properly instruct mammary epithelium during puberty.

scholarly journals Plasma membrane calcium ATPase regulates bone mass by fine-tuning osteoclast differentiation and survival

2012 ◽  
Vol 199 (7) ◽  
pp. 1145-1158 ◽  
Author(s):  
Hyung Joon Kim ◽  
Vikram Prasad ◽  
Seok-Won Hyung ◽  
Zang Hee Lee ◽  
Sang-Won Lee ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Bone Mass ◽  
Osteoclast Differentiation ◽  
Premenopausal Women ◽  
Fine Tuning ◽  
Bone Homeostasis ◽  
Regulatory Loop ◽  
And Function

The precise regulation of Ca2+ dynamics is crucial for proper differentiation and function of osteoclasts. Here we show the involvement of plasma membrane Ca2+ ATPase (PMCA) isoforms 1 and 4 in osteoclastogenesis. In immature/undifferentiated cells, PMCAs inhibited receptor activator of NF-κB ligand–induced Ca2+ oscillations and osteoclast differentiation in vitro. Interestingly, nuclear factor of activated T cell c1 (NFATc1) directly stimulated PMCA transcription, whereas the PMCA-mediated Ca2+ efflux prevented NFATc1 activation, forming a negative regulatory loop. PMCA4 also had an anti-osteoclastogenic effect by reducing NO, which facilitates preosteoclast fusion. In addition to their role in immature cells, increased expression of PMCAs in mature osteoclasts prevented osteoclast apoptosis both in vitro and in vivo. Mice heterozygous for PMCA1 or null for PMCA4 showed an osteopenic phenotype with more osteoclasts on bone surface. Furthermore, PMCA4 expression levels correlated with peak bone mass in premenopausal women. Thus, our results suggest that PMCAs play important roles for the regulation of bone homeostasis in both mice and humans by modulating Ca2+ signaling in osteoclasts.

Modulation of Oxygen Tensions via Microfabricated Devices

2011 ◽  
Author(s):  
Shawn C. Oppegard ◽  
David T. Eddington
Keyword(s):  
Cellular Response ◽  
Tumor Oxygenation ◽  
Low Oxygen ◽  
Oxygen Control ◽  
Precise Control ◽  
Additional Equipment ◽  
Cancer Tumor ◽  
D Cell

Oxygen is a key modulator of many cellular pathways and plays an important role in a number of cellular behaviors. The hypoxic inducible factor 1α (HIF-1α) is often considered the master regulator of the cellular response to oxygen tension (1). HIF-1α is a transcription factor involved in angiogenesis, glucose transport and glycolysis, apoptosis, migration, and differentiation, among many other functions (2). Unfortunately devices permitting in vitro oxygen modulation fail to meet the needs of biomedical research due to the inability to effectively mimic conditions found in vivo. The gold standard for hypoxia work is the hypoxic chamber, but the tool requires hours for equilibration and is not effective at generating very low oxygen levels (3). As an example demonstrating this disadvantage, cancer tumor oxygenation can change in the span of minutes (4). Intermittent hypoxia, or the changing of oxygen over time, has been shown to be important in heart attack, stroke, and sleep apnea as well. Other microfluidic approaches, although offering more oxygen control, are often difficult to disseminate to other labs due to the requirement of specialized methods and equipment for their operation. In this work, a microfabricated technology has been developed to grant precise control the temporal and spatial oxygen concentration exposed to both cell monolayers in the multiwell plate as well as with 3-D cell-seeded constructs. The concept is adaptable to both pre-established and novel experiments depending on the needs of the researcher. The devices are simple to use and require minimal additional equipment beyond what is available to a standard cell culture lab.

scholarly journals Essential Oil Microcapsules Immobilized on Textiles and Certain Induced Effects

Materials ◽  
2019 ◽  
Vol 12 (12) ◽  
pp. 2029 ◽  
Author(s):  
Miruna S. Stan ◽  
Laura Chirila ◽  
Alina Popescu ◽  
Denisa M. Radulescu ◽  
Diana E. Radulescu ◽  
...  
Keyword(s):  
Membrane Integrity ◽  
Dermal Fibroblasts ◽  
Cell Membrane Integrity ◽  
Textile Materials ◽  
Skin Cells ◽  
In Vitro Biocompatibility ◽  
Short Term Exposure ◽  
Before And After

In order to obtain textile materials with potential utility in the development of cosmetic textiles, this study examined the deposition by padding of rose and sage microcapsules on woven textile structures, with different fiber compositions (100% cotton and 50% cotton/50% polyester). Cationization of the textile materials was performed to enhance the degree of uptake the pf the microcapsules on the fabrics’ surface. A commercially acrylate-based binder was used to fix the microcapsules to the textile substrate and to improve the durability against external factors. The finished textile materials were characterized in terms of their physical-mechanical characteristics. The distribution of microcapsules on the fabrics surface before and after five washing cycles and 1000 abrasion cycles was investigated by scanning electron microscopy. The biocompatibility in terms of cell viability, cell membrane integrity and inflammation status of the functionalized fabrics was evaluated on CCD-1070Sk normal human dermal fibroblasts. The cell morphology was evaluated by F-actin staining using fluorescence microscopy and no significant changes were noticed after the incubation in the presence of fabrics compared with control. The in vitro biocompatibility evaluation on human skin cells confirmed the absence of cytotoxicity after the short-term exposure, supporting further in vivo use of these innovative textiles with improved properties.

scholarly journals Advancements and Potential Applications of Microfluidic Approaches—A Review

Chemosensors ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 46 ◽  
Author(s):  
Ishtiaq Ahmed ◽  
Zain Akram ◽  
Mohammed Bule ◽  
Hafiz Iqbal
Keyword(s):  
Modern Science ◽  
Cellular Interactions ◽  
Cellular Microenvironment ◽  
Engineering Research ◽  
Precise Control ◽  
Microfluidic Technology ◽  
Potential Applications ◽  
Micro Level

A micro-level technique so-called “microfluidic technology or simply microfluidic” has gained a special place as a powerful tool in bioengineering and biomedical engineering research due to its core advantages in modern science and engineering. Microfluidic technology has played a substantial role in numerous applications with special reference to bioscience, biomedical and biotechnological research. It has facilitated noteworthy development in various sectors of bio-research and upsurges the efficacy of research at the molecular level, in recent years. Microfluidic technology can manipulate sample volumes with precise control outside cellular microenvironment, at micro-level. Thus, enable the reduction of discrepancies between in vivo and in vitro environments and reduce the overall reaction time and cost. In this review, we discuss various integrations of microfluidic technologies into biotechnology and its paradigmatic significance in bio-research, supporting mechanical and chemical in vitro cellular microenvironment. Furthermore, specific innovations related to the application of microfluidics to advance microbial life, solitary and co-cultures along with a multiple-type cell culturing, cellular communications, cellular interactions, and population dynamics are also discussed.

scholarly journals Bovine Oviduct Epithelial Cell-Derived Culture Media and Exosomes Improve Mitochondrial Health by Restoring Metabolic Flux during Pre-Implantation Development

2020 ◽  
Vol 21 (20) ◽  
pp. 7589
Author(s):  
Tabinda Sidrat ◽  
Abdul Aziz Khan ◽  
Myeon-Don Joo ◽  
Yiran Wei ◽  
Kyeong-Lim Lee ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Embryonic Development ◽  
Metabolic Flux ◽  
Culture Media ◽  
Tca Cycle ◽  
Fine Tuning ◽  
The Tca Cycle ◽  
Oviduct Epithelial Cell

Oviduct flushing is enriched by a wide variety of nutrients that guide the 3–4 days journey of pre-implantation embryo through the oviduct as it develops into a competent blastocyst (BL). However, little is known about the specific requirement and role of these nutrients that orchestrate the early stages of embryonic development. In this study, we aimed to characterize the effect of in vitro-derived bovine oviduct epithelial cell (BOECs) secretion that mimics the in vivo oviduct micro-fluid like environment, which allows successful embryonic development. In this study, the addition of an in vitro derived BOECs-condition media (CM) and its isolated exosomes (Exo) significantly enhances the quality and development of BL, while the hatching ability of BLs was found to be high (48.8%) in the BOECs-Exo supplemented group. Surprisingly, BOECs-Exo have a dynamic effect on modulating the embryonic metabolism by restoring the pyruvate flux into TCA-cycle. Our analysis reveals that Exo treatment significantly upregulates the pyruvate dehydrogenase (PDH) and glutamate dehydrogenase (GLUD1) expression, required for metabolic fine-tuning of the TCA-cycle in the developing embryos. Exo treatment increases the influx into TCA-cycle by strongly suppressing the PDH and GLUD1 upstream inhibitors, i.e., PDK4 and SIRT4. Improvement of TCA-cycle function was further accompanied by higher metabolic activity of mitochondria in BOECs-CM and Exo in vitro embryos. Our study uncovered, for the first time, the possible mechanism of BOECs-derived secretion in re-establishing the TCA-cycle flux by the utilization of available nutrients and highlighted the importance of pyruvate in supporting bovine in vitro embryonic development.

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