Biology subjects

Choi, J.-S.

Publications and source records attributed to Choi, J.-S..

15 recordsLinked to original sources

bioRxiv2026

Predation risk reweights reward preference through coordinated amygdala-prelimbic dynamics

A fundamental challenge for animals and humans is resolving competing survival demands under naturalistic threat, yet circuit-level mechanisms remain poorly understood. We developed a paradigm recapitulating a predator-prey encounter: Long-Evans rats emerged from a nest to forage in an open arena, choosing between preferred and standard reward locations while facing a robotic predator. We simultaneously recorded single-unit activity from the basolateral amygdala (BLA) and the prelimbic cortex (PL). Rats shifted to the safer option under threat. BLA neurons responded predominantly to the predator, whereas PL neurons encoded reward value, threat context, and behavioral state. Population decoding revealed threat encoding in BLA and multiplexed representations in PL. Threat-responsive BLA neurons were preferentially recruited into BLA-PL synchrony before safe choices, and information flow became biased from BLA to PL following predator attack. These findings identify coordinated corticolimbic dynamics as a candidate mechanism through which threat reweights reward-guided action selection under ecological risk.

neuroscience↗

bioRxiv2026

Drinking Motives Synchronize Behavioral and Neural Craving Responses to Alcohol-drinking Videos

Alcohol drinking motives vary among individuals and shape experiences and beliefs about alcohol, influencing the processing of alcohol-related cues. In real-life settings, these cues are contextually rich, amplifying the role of such individualized drinking motives on cue processing. However, previous literature has primarily relied on images of alcohol, which lack contexts and differ significantly from real-life. Here, aiming to investigate real-life craving, we examined the role of alcohol drinking motives in craving in response to naturalistic alcohol-drinking videos. We asked fifty-three problematic alcohol users to speak about their reasons for drinking alcohol to capture unique alcohol drinking motives of each individual. Participants also underwent functional MRI while watching fifteen alcohol-drinking videos, and reported their subjective level of craving and self-relatedness for each video. Behavioral data analysis revealed that individuals with greater alcohol use severity tended to report greater cue-induced craving, but only when they reported that a video was related to themselves. Inter-subject representational similarity analysis showed that participants with similar alcohol drinking motives, reflected in shared drinking reasons and similar self-relatedness to the videos, exhibited synchronized craving-related neural responses during video-watching. Notably, these shared neural processes mediated the link between similar drinking motives and similar self-reported craving levels across participants. Together, our findings highlight the crucial role of alcohol drinking motives in shaping cue-induced alcohol craving, and provide deeper insights into craving in real-world contexts.

neuroscience↗

bioRxiv2026

Microstate-specific functional connectivity in alcohol use disorder using resting-state EEG

Alcohol Use Disorder (AUD) is often described as a "disconnection syndrome", reflecting neural dysfunction associated with chronic alcohol use. However, previous studies on functional connectivity of resting-state EEG (rsEEG) in AUD have reported inconsistent findings--some showing hyperconnectivity, others hypoconnectivity or no significant differences--possibly due to overlooking the brains dynamic nature even at its resting state. Here, we examined rsEEG in 26 young adults with AUD and 35 healthy controls (HC), using microstate analysis to characterize transient brain states and to estimate functional connectivity within each state. We showed that microstate map topologies were comparable between the two groups. However, the temporal dynamics in the AUD group were biased toward microstates C and D, characterized by anterior-to-posterior configurations, within which between-channel functional connectivity differed from that of HC. Particularly within microstate C, the AUD group showed significantly reduced functional connectivity compared to the HC group in the majority of channel pairs. Moreover, compared with conventional functional connectivity estimates, microstate-specific functional connectivity yielded superior classification performance in distinguishing individuals with AUD from HC. Subsequent computation of graph-theoretical measures revealed that individuals with AUD showed less stable hub-like properties and reduced small-worldness in microstate C, indicating diminished network efficiency. Our findings suggest that transient EEG properties, exemplified by microstate-specific functional connectivity, provide informative neural markers for characterizing the impact of alcohol use on the brain. HighlightsO_LIResting-state EEG microstates reveal altered brain dynamics in alcohol use disorder C_LIO_LIMicrostate C exhibits widespread reductions in functional connectivity in AUD C_LIO_LIMicrostate-specific connectivity outperforms conventional measures in AUD classification C_LIO_LIGraph analysis reveals reduced network efficiency and unstable hubs in AUD C_LI

neuroscience↗

bioRxiv2025

Cryo-EM structures of an anti-MLC1 Fab in apo and peptide-bound states reveal the structural basis of antigen recognition

Monoclonal antibodies are indispensable tools in structural biology and biomedical research, but defining the molecular basis of their specificity remains challenging. Here, we developed a novel monoclonal antibody (37E5) against the astrocytic membrane protein MLC1, a component of gliovascular signaling implicated in megalencephalic leukoencephalopathy with subcortical cysts. 37E5 demonstrated high specificity and versatility across biochemical, cellular, and histological assays, enabling reliable detection of MLC1 in both human and mouse tissue. Using single-particle cryo-EM, we determined [~]3 [A] resolution structures of the 37E5 Fab in apo and antigen-bound states, despite the small molecular mass ([~]50 kDa), close to the lower size limit of cryo-EM. The antigen-bound structure revealed continuous density for an MLC1-derived peptide and enabled atomic mapping of polar and non-polar interaction networks. Conformational changes in CDR-L1 and CDR-L2 indicated an induced-fit mechanism of recognition. Comparison with AlphaFold-predicted models underscored the accuracy of Fab backbone prediction but revealed major limitations in modeling epitope-paratope geometry. These findings establish 37E5 as a versatile antibody for mechanistic studies of gliovascular biology and MLC disease, while demonstrating that cryo-EM can achieve atomic-level characterization of small Fab-antigen complexes, thereby expanding the methodological frontier of antibody-antigen structural biology. SignificanceThis study defines the molecular basis of MLC1 recognition by a novel monoclonal antibody, establishes 37E5 as a versatile reagent for mechanistic and translational research, and demonstrates the feasibility of cryo-EM to resolve dynamic features of small Fab-antigen complexes.

biochemistry↗

bioRxiv2025

Electrochemical Metabolic Profiling Reveals Mitochondrial Hyperactivation and Enhanced Neural Progenitor Proliferation in MLC1-Mutant Human Cortical Organoids

Mitochondrial function is critical for neural progenitor regulation, yet its dysregulation during early human brain development remains poorly defined. Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a neurodevelopmental disorder caused by MLC1 mutations, previously attributed to postnatal astrocyte dysfunction. Using patient-derived human cortical organoids, we show that MLC1 is expressed in early neuroepithelial cells. To assess mitochondrial state in live organoids, we developed the MAGO (Matrigel-coated gold nanostructure) platform for real-time, label-free detection of redox activity. MLC1 mutant organoids showed mitochondrial hyperactivation, increased ATP and ROS, reduced membrane potential, and altered fusion protein expression. These changes were accompanied by enhanced BrdU incorporation and expansion of PAX6/SOX2 progenitors. To assess the causal role of MLC1 mutation, we generated isogenic organoids using CRISPR prime editing, which recapitulated redox hyperactivation and increased proliferation. Our findings redefine MLC as a disorder of early mitochondrial and progenitor dysregulation and establish a tractable platform to study metabolic mechanisms in neurodevelopmental disease.

neuroscience↗

bioRxiv2024

HSP90 interacts with VP37 to facilitate the cell-to-cell movement of broad bean wilt virus 2

The systemic spread of viruses in plants requires successful viral cell-to-cell movement through plasmodesmata (PD). Viral movement proteins (MPs) interact with cellular proteins to modify and utilize host transport routes. Broad bean wilt virus 2 (BBWV2), a widespread plant RNA virus, moves from cell to cell as a virion through the PD gated by VP37, the MP of BBWV2. However, the host proteins that function in the cell-to-cell movement of BBWV2 remain unclear. In this study, we identified cellular heat shock protein 90 (HSP90) as an interacting partner of VP37. The interaction between HSP90 and VP37 was assessed using the yeast two-hybrid assay, co-immunoprecipitation, and bimolecular fluorescence complementation. Tobacco rattle virus-based virus-induced gene silencing analysis revealed that HSP90 silencing significantly inhibited the systemic spread of BBWV2 in N. benthamiana plants. Furthermore, in planta treatment with geldanamycin (GDA), an inhibitor of the chaperone function of HSP90, demonstrated the necessity of HSP90 in successful cell-to-cell movement and systemic infection of BBWV2. Interestingly, GDA treatment inhibited the HSP90-VP37 interaction at the PD, resulting in the inhibition of VP37-derived tubule formation through the PD. Our results suggest that the HSP90-VP37 interaction regulates VP37-derived tubule formation through the PD, thereby facilitating the cell-to-cell movement of BBWV2. IMPORTANCEThis study highlights the regulatory role of heat shock protein 90 (HSP90) in facilitating the cell-to-cell movement of broad bean wilt virus 2 (BBWV2). HSP90 interacted with VP37, the movement protein of BBWV2, specifically at plasmodesmata (PD). This study demonstrated that the HSP90-VP37 interaction is crucial for viral cell-to-cell movement and the formation of VP37-derived tubules, which are essential structures for virus transport through the PD. The ATP-dependent chaperone activity of HSP90 is integral to this interaction, as demonstrated by the inhibition of virus movement upon treatment with geldanamycin (GDA), which disrupts the function of HSP90. These findings elucidate the molecular mechanisms underlying the cell-to-cell movement of plant viruses, and highlight the role of HSP90 in viral infection. This study suggests that the chaperone activity of HSP90 may function in changing the conformational structure of VP37, thereby facilitating the assembly and function of virus-induced structures required for viral cell-to-cell movement.

microbiology↗

bioRxiv2024

Parabrachial CGRP neurons modulates conditioned active defensive behavior under a naturalistic threat

Recent studies suggest that calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) represent aversive information and signal a general alarm to the forebrain. If CGRP neurons serve as a true general alarm, activation of CGRP neurons can trigger either freezing or fleeing defensive behavior, depending on the circumstances. However, the majority of previous findings have reported that CGRP neurons modulate only freezing behavior. Thus, the present study examined the role of CGRP neurons in active defensive behavior, using a predator-like robot programmed to chase mice in fear conditioning. Our electrophysiological results showed that CGRP neurons encoded the intensity of various unconditioned stimuli (US) through different firing durations and amplitudes. Optogenetic and behavioral results revealed that activation of CGRP neurons in the presence of the chasing robot intensified fear memory and significantly elevated conditioned fleeing behavior during recall of an aversive memory. Animals with inactivated CGRP neurons exhibited significantly low levels of fleeing behavior even when the robot was set to be more threatening during conditioning. Our findings expand the known role of CGRP neurons in the PBN as a crucial part of the brains alarm system, showing they can regulate not only passive but also active defensive behaviors.

neuroscience↗

bioRxiv2024

Unraveling the Complexity of Abdominal Aortic Aneurysm: Multiplexed Imaging Insights into C-Reactive Protein-Related Variations

BackgroundAbdominal aortic aneurysm (AAA) is a potentially lethal condition that often remains asymptomatic until it ruptures. Recent research suggests that immune-inflammatory processes are associated with AAA development, yet the exact mechanisms remain unclear. Serum C-reactive protein (CRP) serves as a prognostic marker for AAA and various cardiovascular diseases. When CRP accumulates in damaged tissues, it transforms into a monomeric form, exacerbating tissue damage. Our previous study confirmed the presence of CRP deposition in eroded AAA and atherosclerosis regions, accompanied by an increased infiltration of inflammatory cells. However, a comprehensive understanding of the specific changes in the inflammatory cellular landscape attributable to CRP deposition is lacking. Here, we aimed to explore cellular-level alterations in AAAs associated with varying CRP levels. MethodsWe categorized AAA patients into High-CRP ([≥]0.1 mg/dL, and [≥]3+ CRP IHC score, n=6) and Low-CRP ([≤]0.1 mg/dL, and [≤]1+ CRP IHC score, n=3), and used normal aorta specimens as a baseline control. The cellular landscape of immune and stromal components was characterized using Co-Detection by Indexing (CODEX) tissue imaging with 31 DNA-barcoded antibodies, followed by single-cell-based analysis and GPU-accelerated unsupervised clustering. ResultsWe identified 51 distinct immune and stromal cell types in the cohort and revealed significant differences in protein expression patterns among the groups. In AAA, stromal cells decreased significantly, while immune cell proportions sharply increased. Lag3+ T cell regulators decreased, leading to an increase in CD3+ T cells. The composition of immune cells within atherosclerotic plaques was associated with the degree of CRP deposition in AAA. The High-CRP group showed increased M1 and Ki67+ proliferating macrophages, while the Low-CRP group exhibited intensified fibrosis with M2 macrophages. ConclusionsOur study found significant variations in immune cell distribution within AAA walls based on CRP levels. These findings suggest a potential link between CRP-related immune changes and AAA progression. HIGHLIGHTSO_LIBy performing CODEX (co-detection by indexing) multiplexed imaging on paraffin-embedded, formalin-fixed archived abdominal aortic aneurysm (AAA) tissue samples with varying CRP levels, we segmented 415,365 cells into 51 distinct clusters. C_LIO_LIIn AAA, the presence of CRP deposition led to variations in the spatial relationships, distances, and enrichment patterns among immune and stromal cells.. C_LIO_LIIn AAA-High CRP, there was an intensified infiltration of M1 macrophages and various immune cells observed in the atherosclerotic plaque. C_LIO_LIIn AAA-Low CRP, severe stromal fibrosis was associated with M2 macrophages. C_LIO_LIOur results suggest that the deposition of CRP into the atherosclerotic plaque alters the immune-stromal landscape in AAA. C_LI

pathology↗

bioRxiv2023

Population analyses reveal heterogenous encoding in the medial prefrontal cortex during naturalistic foraging

Foraging in the wild requires coordinated switching of critical functions, including goal-oriented navigation and context-appropriate action selection. Nevertheless, few studies have examined how different functions are represented in the brain during naturalistic foraging. To address this question, we recorded multiple single-unit activities from the medial prefrontal cortex (mPFC) of rats seeking a sucrose reward in the presence of an unpredictable attack posed by a robotic predator (Lobsterbot). Simultaneously recorded ensemble activities from neurons were analyzed in reference to various behavioral indices as the animal moved freely across the foraging area (F) between the nest (N) and the goal (E) area. An artificial neural network, trained with simultaneously recorded neural activity, estimated the rats current distance from the Lobsterbot. The accuracy of distance estimation was the highest in the middle F-zone in which the dominant behavior was active navigation. The spatial encoding persisted in the N-zone when non-navigational behaviors such as grooming, rearing, and sniffing were excluded. In contrast, the accuracy decreased as the animal approached the E-zone, when the activity of the same neuronal ensembles was more correlated with events related to dynamic decision-making between food procurement and Lobsterbot evasion. A population-wide analysis confirmed highly heterogeneous encoding by the region. To further assess the decision-related activity in the E-zone, a naive Bayesian classifier was trained to predict the success and failure of avoidance behavior. The classifier predicted the avoidance outcome as much as 6 s before the head withdrawal. In addition, two sub-populations of recorded units with distinct temporal dynamics contributed differently to the prediction. These findings suggest that an overlapping population of mPFC neurons may switch between two heterogenous modes, encoding relevant locations for goal-directed navigation or an imminent situational challenge.

neuroscience↗

bioRxiv2023

14K Prolactin Derived 14-Mer Antiangiogenic Peptide Targets Bradykinin-/Nitric Oxide-cGMP-Dependent Angiogenesis

VEGF-targeted antiangiogenic therapy for cancers has been principally used but also faced a limitation due to resistance and adverse effects in clinical application. This observation further endorses the need for novel anti-angiogenesis molecules and/or understanding of the mechanisms of tumor angiogenesis before clinical trial. In the present study, we investigated the antiangiogenic properties of a novel 14-mer antiangiogenic peptide (14-MAP) derived from N-terminal 14kDa buffalo prolactin, followed by an exploration of its mode of action. 14-MAP at the picomolar concentration inhibited VEGF- and bradykinin (an autacoid peptide expressed in vascular tissues in pathophysiology)-stimulated endothelial nitric oxide (eNO) production, cell migration and proliferation in endothelial cells and vessel development in chick embryo. The crucial inhibitory effects of the peptide, however, were presented on the bradykinin-dependent angiogenic properties. Moreover, the interference of 14-MAP with the eNO synthase (eNOS)-cyclic GMP pathway was identified. A combination of low dose of Avastin, a widely used drug targeting VEGF-dependent angiogenesis, and 14-MAP significantly reduced tumor size in a mouse model of human colon cancer. These results suggest that 14-MAP, a bradykinin- and eNOS-dependent antiangiogenic peptide, can be useful for overcoming the limitation of VEGF-targeted antiangiogenic therapy in cancer patients.

cancer biology↗

bioRxiv2020

CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm

ObjectiveThe molecular mechanisms of the degeneration of the aortic wall in abdominal aortic aneurysm (AAA) are poorly understood. The monomeric form of C-reactive protein (mCRP) is deposited in damaged cardiovascular organs and aggravates the prognosis; however, it is unknown whether mCRP is deposited in the degenerated aorta of abdominal aortic aneurysm (AAA). We investigated whether mCRP is deposited in AAA and examined the associated pathogenic signaling pathways. MethodsTwenty-four cases of AAA were analyzed and their histological features were compared according to the level of serum CRP and the degree of mCRP deposition. Proteomic analysis was performed in AAA cases with strong and diffuse CRP immunopositivity (n=7) and those with weak, focal, and junctional CRP immunopositivity (n=3). ResultsmCRP was deposited in the aortic specimens of AAA in a characteristic pattern that coincided with the lesion of the diminished elastic layer of the aortic wall. High serum CRP level was associated with stronger mCRP immunopositivity and a larger maximal diameter of aortic aneurysm. Proteomic analysis in AAA showed that multiple proteins were differentially expressed according to mCRP immunopositivity. Also, ingenuity pathway analysis showed that pathways associated with atherosclerosis, acute phase response, complement system, immune system, and coagulation were enriched in AAA cases with high mCRP immunopositivity. ConclusionsAAA showed a characteristic deposition of mCRP, and multiple potentially pathologic signaling pathways were upregulated in AAA cases with strong CRP immunopositivity. mCRP and the aforementioned pathological pathways may serve as targets for managing the progression of AAA.

pathology↗

bioRxiv2020

Role of ischemic preconditioning in cardioprotective mechanisms of mCRP deposited myocardium in a rat model

The deposition of monomeric C-reactive protein (mCRP) in the myocardium aggravates ischemia-reperfusion injury (IRI) and myocardial infarction. Ischemic preconditioning (IPC) is known to protect the myocardium against IRI. We evaluated the effects of IPC on mCRP-deposited myocardium due to IRI in a rat model. Myocardial IRI was produced by ligation of the coronary artery. Direct IPC was applied before IRI using multiple short direct occlusions of the coronary artery. CRP was infused intravenously after IRI. The study groups included the following: sham (n=3), IRI only (n=5), IRI+CRP (n=9), and IPC+IRI+CRP (n=6) groups. The infarct area and area at risk were assessed using Evans blue and 2,3,5-triphenyltetrazolium chloride (2,3,5-TTC) staining. Additionally, mCRP immunostaining and interleukin (IL)-6 mRNA reverse transcriptase-polymerase chain reaction (RT-PCR) were performed. In the IRI+CRP group, the infarcted area, mCRP deposition, and IL-6 mRNA expression were higher than those in the IRI only group. However, in the IPC+IRI+CRP group, the infarction (20% vs. 34% p=0.085) and mCRP myocardial deposition (21% vs. 44%, p=0.026) were lower and IL-6 mRNA expression was higher than those in the IRI+CRP group (fold change, 407 vs. 326, p=0.808), although this was not statistically significant. IPC has cardioprotective effects against myocardial damage caused by mCRP deposition. This protective effect is related to the increase in IL-6 mRNA expression.View Full Text

pathology↗

bioRxiv2019

Marker subset selection and decision support range identification for acute myeloid leukemia classification model development with multiparameter flow cytometry

In this study, we developed acute myeloid leukemia (AML) classification model through Wilks lambda-based important marker-identification method and stepwise-forward selection approach, and spotted important decision-support range of flow-cytometry parameter using insights provided by machine-learning algorithm. AML flow-cytometry data released from FlowCAP-II challenge in 2011 was used. In FlowCAP-II challenge, several sample classification algorithms were able to effectively classify AML and non-AML. Most algorithms extracted features from high-dimensional flow-cytometry readout comprised of multiple fluorescent parameters for a large number of antibodies. Multiple parameters with forward scatter and side scatter increase computational complexity in the feature-extraction procedure as well as in the model development. Parameter-subset selection can decrease model complexity, improve model performance, and contribute to a panel design specific for target disease. With this motivation, we estimated importance of each parameter via Wilks lambda and then identified the best subset of parameters using stepwise-forward selection. In the importance-estimation process, histogram matrix of each parameter was used. As a result, parameters, which are associated with blasts gating and identification of immature myeloid cells, were identified as important descriptors in AML classification, and combination of these markers is more effective than an individual marker. A random-forest, supervised-classification machine-learning algorithm was used for the model development. We highlighted decision-support range of the fluorescent signal for the identified important parameters, which significantly contribute to AML classification, through a mean decrease in Gini supported in random forest. These specific ranges could help with establishing diagnosis criteria and elaborate the AML classification model. Because methodology proposed in this study can not only estimate the importance of each parameter but also identify the best subset and the specific ranges, we expect that it would contribute to in silico modeling using flow- and mass-cytometry readout as well as panel design for sample classification.\n\nAuthor summaryFlow cytometry is a widely used technique to analyze multiple physical characteristics of an individual cell and diagnose and monitor human disease as well as response to therapy. Recent developments in hardware (multiple lasers and fluorescence detectors), fluorochromes, and antibodies have facilitated the comprehensive and in-depth analysis of high numbers of cells on a single cell level and led to the creation of various computational analysis methods for cell type identification, rare cell identification, and sample classification. Flow cytometry typically uses panels with a large number of antibodies, leading to high-dimensional multiparameter flow cytometry readout. It increases computational complexity and makes interpretation difficult. In this study, we identified the best subset of the parameters for AML classification model development. The subset would contribute to panel design specific for the target disease and lead to easy interpretation of the results. In addition, we spotted important decision-support range of flow-cytometry parameter via insights provided by machine-learning algorithm. We expect that profiling information of fluorescence expression over the identified decision-support range would complement existing diagnosis criteria.

bioinformatics↗

bioRxiv2019

Identification of Ca-rich dense granules in human platelets using scanning transmission X-ray microscopy

Whole mount (WM) platelet preparations followed by transmission electron microscopy (TEM) observation is the standard method currently used to assess dense granule (DG) deficiency (DGD). However, due to electron density-based contrast mechanism in TEM, other granules such as -granules might cause false DGs detection. Herein, scanning transmission X-ray microscopy (STXM), was used to identify DGs and minimize false DGs detection of human platelets. STXM image stacks of human platelets were collected at the calcium (Ca) L2,3 absorption edge and then converted to optical density maps. Ca distribution maps obtained by subtracting the optical density map at pre-edge region from those obtained at post-edge region were used for identification of DGs based on richness of Ca. Dense granules were successfully detected by using STXM method without false detection based on Ca maps for 4 human platelets. Spectral analysis of granules in human platelets confirmed that DGs contained richer Ca content than other granules. Image analysis of Ca maps provided quantitative parameters which would be useful for developing image-based DG diagnosis models. Therefore, we would like to propose STXM as a promising approach for better DG identification and DGD diagnosis, as a complementary tool to the current WM TEM approach.

biophysics↗

bioRxiv2019

Mass Cytometry Study on the Heterogeneity in Cellular Association and Cytotoxicity of Silver Nanoparticles in Human Immune Cells

There have been many reports about the adverse effects of nanoparticles (NPs) on the environment and human health. Conventional toxicity assessments of NPs frequently assume uniform distribution of monodisperse NPs in homogeneous cell populations, and provide information on the relationships between the administered dose of NPs and cellular responses averaged for a large number of cells. They may have limitations in describing the wide heterogeneity of cell-NP interactions, caused by cell-to-cell and NP-to-NP variances. To achieve more detailed insight into the heterogeneity of cell-NP interactions, it is essential to understand the cellular association and adverse effects of NPs at single-cell level. In this study, we applied mass cytometry to investigate the interactions between silver nanoparticles (AgNPs) and primary human immune cells. High dimensionality of mass cytometry allowed us to identify various immune cell types and observe the cellular association and toxicity of AgNPs in each population. Our findings showed that AgNPs had higher affinity with phagocytic cells like monocytes and dendritic cells and caused more severe toxic effects than with T cells, B cells and NK cells. Multi-element detection capability of mass cytometry also enabled us to simultaneously monitor cellular AgNP dose and intracellular signaling of individual cells, and subsequently investigate the dose-response relationships of each immune population at single-cell level, which are often hidden in conventional toxicity assays at bulk-cell level. Our study will assist future development of single-cell dose-response models for various NPs and will provide key information for the safe use of nanomaterials for biomedical applications.

biochemistry↗