Biology subjects

Dhar, S.

Publications and source records attributed to Dhar, S..

21 records · Page 2Linked to original sources

bioRxiv2019

The repertoire of serous ovarian cancer non-genetic heterogeneity revealed by single-cell sequencing of normal fallopian tube epithelial cells

The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH can be accurately measured when informed by the molecular signatures of the normal cells of origin. We surveyed the transcriptomes of [~] 4000 normal fallopian tube epithelial (FTE) cells, the cells of origin of serous ovarian cancer (SOC), and identified six FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH that was previously unrecognized. Importantly, NGH-based stratification of [~]1700 tumors robustly predicted survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.\n\nHighlightsO_LIThe projection of FTE subtypes refines the molecular classification of serous OC\nC_LIO_LIComprehensive single-cell profiling of FTE cells identifies 6 molecular subtypes\nC_LIO_LISubstantial non-genetic heterogeneity of HGSOC identified in 1700 tumors\nC_LIO_LIA mesenchymal-high HGSOC subtype is robustly correlated with poor prognosis\nC_LI

cancer biology↗

bioRxiv2018

Role of Physicochemical Properties of Protein in Modulating the Nanoparticle-Bio interface

Nanoparticles, on exposure to the biological milieu, tend to interact with macromolecules to form a biomolecular corona. The biomolecular corona confers a unique biological identity to nanoparticles, and its protein composition plays a deterministic role in the biological fate of nanoparticles. The physiological behavior of proteins stems from their physicochemical aspects including surface charge, hydrophobicity, and structural stability. However, there is insufficient understanding about the role of physicochemical properties of proteins in biomolecular corona formation. We hypothesized that the physicochemical properties of proteins would influence their interaction with nanoparticles and have a deterministic effect on nanoparticle-cell interactions. To test our hypothesis, we used model proteins from different structural classes to understand the effect of secondary structure elements of proteins on the nanoparticle-protein interface. Further, we modified the surface of proteins to study the role of protein surface characteristics in governing the nanoparticle-protein interface. For this study, we used mesoporous silica nanoparticles as a model nanoparticle system. We observed that the surface charge of proteins governs the nature of the primary interaction as well as the extent of subsequent secondary interactions causing structural rearrangements of the protein. We also observed that the secondary structural contents of proteins significantly affected both the extent of secondary interactions at the nanoparticle-protein interface and the dispersion state of the nanoparticle-protein complex. Further, we also studied the interactions of different protein-coated nanoparticles with different types of cell (fibroblast, carcinoma, and macrophage). We observed that different cells internalized nanoparticle-protein complex as a function of secondary structural components of the protein. The type of model protein had a significant effect on their internalization by macrophages. Overall, we observed that the physicochemical characteristics of proteins had a significant role in modulating the nanoparticle-bio-interface at the level of both biomolecular corona formation and nanoparticle internalization by cells.

bioengineering↗

bioRxiv2018

Quantitative Estimation of Long-Range Interactions at the Nanoscale

Nano-bio interfaces attune nanoparticle-mediated biological responses. The nano-bio interface, like all interfacial interactions, is governed by non-covalent long-range interactions (LRIs). These LRIs include electrostatic, electrodynamic and acid-base interactions. There is a lack of understanding about the contribution of LRIs at the nano-bio interface for want of suitable methods for the estimation of dispersive, acidic, and basic components of the surface tension of nanoparticles. To address this, we developed an experimental and theoretical framework for the estimation of surface tension components of nanoparticles and biomacromolecules by partitioning them in a biphasic system. The work presented here is the first instance in the literature for estimating the surface tension components of nanoparticles and biomacromolecules suspended in aqueous suspensions. We also observed that LRIs have a deterministic role in biologically relevant phenomena such as salt-induced nanoparticle agglomeration and protein-nanoparticle interaction. Collectively, the results presented in this work provide a rapid and inexpensive framework for predicting the energetics of nanoparticle-nanoparticle and nanoparticle-protein interactions by estimating average ensemble surface characteristics like surface tension and surface charge density.

bioengineering↗