Biology subjects

Bhatia, D. D.

Publications and source records attributed to Bhatia, D. D..

6 recordsLinked to original sources

bioRxiv2022

Green emitting carbon quantum dots (GCQDs) to probe endocytic pathways in cells; for tissue and in vivo bioimaging

Small sized, carbon-based organic nanoparticles have recently gained attention due their advantage of biocompatibility, photostability and biological non-toxicity as compared to their inorganic counterparts. Herein, a new class of small (5-8 nm), green emitting fluorescent carbon quantum dots (GCQDs) were synthesized using organic substrates like citric acid and ascorbic acid in aqueous solvent containing water and ethanol. The very small size and bright green photoluminescence prompted their use for both in vitro and in vivo bioimaging. GCQDs were uptaken via clathrin mediated pathways in mouse kidney and liver primary cells. Similarly, they showed active uptake and distribution in the zebrafish embryo model system. The optical tunability and surface modification properties of these GCQDs provide a platform to be explored for them to emerge as a new class of targeted bioimaging entities, as well as tools for biomedical applications.

bioengineering↗

bioRxiv2022

Hypoxia modulates cellular endocytic pathways and organelles with enhanced cell migration and 3D cell invasion

Hypoxia, a decrease in cellular or tissue level oxygen content, is characteristic of most tumours and shown to drive cancer progression by altering multiple subcellular processes. We hypothesized that the cancer cells in a hypoxic environment might have slower proliferation rates and increased invasion and migration rate with altered endocytosis when compared to the cancer cells in the periphery of the tumour mass that experiences normoxic condition. Using chemically induced hypoxia, a short hypoxic exposure increased the uptake of clathrin independent endocytic marker Galectin-3, but a prolonged hypoxic exposure decreased clathrin-independent endocytic uptake, while clathrin mediated endocytosis remained unaffected. Subcellular organelles such as mitochondria showed enhanced intensity to withstand the hypoxic stress, while other organelles such as ER were significantly decreased. The proliferation rates decreased, and the migration and invasion rate increased in cancer cells in hypoxic condition compared to normoxic cancer cells.These data suggest that hypoxia modulates cellular endocytic pathways with decreased proliferation and enhanced cell migration and invasion. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/480665v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@56841corg.highwire.dtl.DTLVardef@1fb82dborg.highwire.dtl.DTLVardef@14c3253org.highwire.dtl.DTLVardef@17c0381_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2022

Self-assembled DNA nanostructures promote cell migration & differentiation of human umbilical vein endothelial cells

DNA nanostructures have been explored for capabilities to influence cellular behavior and its functions. Recent times have seen the development of new emergent functionalities of DNA nanodevices as class of biomaterials with immense capacity to interface with biological systems and having vast potential in disease diagnosis and therapeutics. Being chemically robust and biocompatible in nature, DNA nanostructures have been surface modified and structurally fine-tuned to find emerging applications in the field of stem cell therapy and tissue regeneration. DNA nanostructures can be utilized for therapeutic angiogenesis that involves induction of blood vessel formation and can be used to treat ischemic diseases like stroke or heart failure. This work addresses the effect of DNA nanostructures structural topology in their capacity to stimulate endothelial cells angiogenesis. We tested a panel of four geometries of DNA nanostructure and checked their potential on the differentiation of human umbilical vein endothelial cells (HUVECs). While different DNA nanostructure geometries showed successful angiogenesis induction and cell migration in HUVECs, tetrahedral DNA cages showed the maximum uptake and angiogenesis potential indicating that not only the composition of materials, but also the 3D arrangement of ligands might also play role in stimulating the angiogenesis process.

bioengineering↗

bioRxiv2021

Ligand geometry dictates cellular and in vivo uptake of 3D DNA nanostructures

Fabrication of nanoscale DNA devices to generate 3D nano-objects with precise control of shape, size, and presentation of ligands has shown tremendous potential for therapeutic applications. The interactions between different topologies of 3D DNA nanostructures and the cell membranes are crucial for designing efficient tools for interfacing DNA devices with biological systems. The practical applications of these DNA nanocages are still limited in cellular and biological systems owing to the limited understanding of interactions of different surface topologies of DNA nanodevices with cell membranes. The correlation between the geometry of DNA nanostructures and their internalization efficiency remains elusive. We investigated the influence of the shape and size of 3D DNA nanostructure on their cellular internalization efficiency. We found that of different geometries designed, one particular geometry, i.e., the tetrahedral shape, is more favoured over other geometries for their cellular uptake in 2D and 3D cell models. This is also replicable for cellular processes like 3D cell invasion assays in 3D spheroid models and passing the epithelial barriers in in-vivo zebrafish model systems. Our work establishes ground rules for the rational designing of DNA nanodevices for their upcoming biological and biomedical applications.

bioengineering↗

bioRxiv2021

DESIGNER DNA HYDROGELS TO STIMULATE 3D CELL INVASION BY ENHANCED RECEPTOR EXPRESSION AND MEMBRANE ENDOCYTOSIS

DNA has emerged as one of the smartest biopolymers to bridge the gap between chemical science and biology to design scaffolds like hydrogels by physical entanglement or chemical bonding with remarkable properties. We present here a completely new application of DNA based hydrogels in terms of their capacity to stimulate membrane endocytosis, leading to enhanced cell spreading and invasion for cells in ex-vivo 3D spheroids models. Multiscale simulation studies along with DLS data showed that the hydrogel formation was enhanced at lower temperature and it converts to liquid with increase in temperature. DNA hydrogels induced cell spreading as observed by increase in cellular area by almost two-folds followed by increase in receptor expression, endocytosis and 3D invasion potential of migrating cells. Our first results lay the foundation for upcoming diverse applications of hydrogels to probe and program various cellular and physiological processes that can have lasting applications in stem cells programming and regenerative therapeutics.

bioengineering↗

bioRxiv2021

Water soluble, red emitting, carbon nanoparticles stimulate 3D cell invasion via clathrin-mediated endocytic uptake

Bright, fluorescent nanoparticles with excitation and emission towards the red end of the spectrum are highly desirable in the field of bioimaging. We present here a new class of organic carbon-based nanoparticles (CNPs) with robust quantum yield and fluorescence towards the red region of the spectrum. Using organic substrates like para-phenylenediamine (PPDA) dispersed in diphenyl ether and reflux conditions, we achieved scalable amounts of CNPs of the average size of 25 nm. These CNPs were readily uptaken by different mammalian cells, and we show that they prefer clathrin-mediated endocytosis for their cellular entry route. Not only can these CNPs be specifically uptaken in cells, but they also stimulate cellular processes like cell invasion from 3D spheroid models. These new class of CNPs, which have sizes similar to proteinaceous ligands, hold immense potential for their surface functionalization, whereby they could be explored as promising bioimaging agents for biomedical imaging and intracellular drug delivery.

bioengineering↗