Biology subjects

Ma, G.

Publications and source records attributed to Ma, G..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Regional Glymphatic Dysfunction is linked to Spinocerebellar Ataxia Type 3 pathophysiology

Spinocerebellar ataxia type 3 (SCA3) involves neuroinflammation and imbalance between production and clearance of proteins which affects the glymphatic system, the lymphatic-like, fluid-transport system in the brain. However, it is unclear whether SCA3 is related to impairments in glymphatic function. Using multimodal imaging data, 34 SCA3 patients and 36 age-, sex- and educational matched healthy controls (HCs) were compared using multiple glymphatic measurements, including choroid plexus (CP) and cerebrospinal fluid (CSF) volume, diffusion tensor imaging along the perivascular (DTI-ALPS) index, and coupling relationship between blood-oxygen-level-dependent signals and CSF flow (BOLD-CSF coupling). Then, we evaluated regional glymphatic function by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, posterior, and cerebellum regions, thereby identifying the spatial variation of glymphatic function in the two groups. We demonstrated that compared with HCs, larger CP and CSF volumes were found in SCA3 patients. More importantly, for DTI-ALPS index and BOLD-CSF coupling, these surrogate markers for glymphatic clearance were weaker in SCA3 patients. Furthermore, altered regional glymphatic functions were most prominent in midbrain, cerebellum and middle regions. Crucially, the altered midbrain, cerebellum, middle and global glymphatic functions were accompanied by the severity of ataxia and other SCA3 symptoms. Similar to other neurodegenerative disorders, the association between multiple glymphatic indexes and SCA3 symptoms suggested that waste clearance is disrupted in SCA3 patients, which shed light on the pathogenesis of this disease from a glymphatic lens. Our findings highlighted the dysregulated glymphatic function as a novel diagnostic marker for SCA3.

neuroscience↗

bioRxiv2024

BRD8 guards the pluripotent state by sensing and maintaining histone acetylation

Epigenetic control of cell fates is a critical determinant to maintain cell type stability and permissive differentiation. However, the epigenetic control mechanisms are not well understood. Here, we show that the histone acetyltransferase reader protein BRD8 impairs the conversion of primed mouse EpiSCs (epiblast stem cells) to naive mouse ESCs (embryonic stem cells). BRD8 works by maintaining histone acetylation on promoters and transcribed gene bodies. BRD8 is responsible for maintaining open chromatin at somatic genes, and histone acetylation at naive-specific genes. When Brd8 expression was reduced, chromatin accessibility was unchanged, but histone acetylation at primed-specific genes was reduced. Conversely, naive-specific genes had reduced repressive chromatin marks, and acquired accessible chromatin more rapidly during the cell type conversion. We show that this process requires active histone deacetylation to promote the conversion of primed to naive. Our data supports a model for BRD8 reading histone acetylation to accurately localize the genome-wide binding of the histone acetyltransferase KAT5. Overall, this study shows how the reading of the histone acetylation state by BRD8 maintains cell type stability. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/585857v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@199139forg.highwire.dtl.DTLVardef@d735c6org.highwire.dtl.DTLVardef@10b6e15org.highwire.dtl.DTLVardef@16863cf_HPS_FORMAT_FIGEXP M_FIG C_FIG Key findingsO_LIBRD8 blocks the primed-to-naive transition. C_LIO_LIReduced Brd8 promoted the suppression of somatic and primed genes through reduced chromatin repression. C_LIO_LIReduced Brd8 enabled the accelerated activation of naive-specific genes by opening chromatin. C_LIO_LIBRD8 anchors the histone acetyltransferase KAT5 to acetylated genomic loci. C_LI

cell biology↗

bioRxiv2023

The effect of problem-based learning on improving problem-solving, self-directed learning, and critical thinking ability for the pharmacy students

ObjectiveThis study aimed to comprehensively evaluate the effect of PBL on problem-solving, self-directed learning, and critical thinking ability of pharmaceutical students through a randomized controlled trial (RCT) and meta-analysis of RCTs. MethodsIn 2021, 57 third-year pharmacy students from China Pharmaceutical University were randomly divided into a PBL group and a lecture-based learning (LBL) group. Mean scores were compared between the two groups for problem-solving, self-directed learning, communication skills, critical thinking, and final exam grades. Students feedback on the implementation of PBL was also collected. A meta-analysis was subsequently performed on eight studies involving 1,819 students. ResultsThe PBL group had significantly higher mean scores for problem-solving (8.43{+/-}1.56) and self-directed learning (7.39{+/-}1.19) than the LBL group (7.02{+/-}1.72 and 6.41{+/-}1.28, respectively). The PBL group also showed better communication skills (8.86{+/-}1.47) than the LBL group (7.68{+/-}1.89). The mean level of critical thinking was significantly higher in the PBL group than the LBL group (p=0.02). The PBL group also had better final exam grades (79.86{+/-}1.38) compared to the LBL group (68.1{+/-}1.76). Student feedback on PBL implementation was positive. The subsequent meta-analysis confirmed these findings. ConclusionThis study found that PBL is an effective teaching method for pharmacy students.

scientific communication and education↗

bioRxiv2023

Rapid degeneration and neurochemical plasticity of the lateral geniculate nucleus following lesions of the primary visual cortex in marmoset monkeys

Lesions of the primary visual cortex (V1) cause retrograde neuronal degeneration, volume loss and neurochemical changes in the lateral geniculate nucleus (LGN). Here we characterise the timing of these processes, by comparing the LGN of adult marmoset monkeys following various recovery times after unilateral V1 lesions. Observations in NeuN-stained sections obtained from animals with very short (3 days) recoveries showed that the volume and neuronal density in the LGN ipsilateral to the lesions were similar to those in the contralateral hemispheres. However, neuronal density in the LGN lesion projection zones (LPZ) dropped rapidly thereafter, with a loss of [~]50% of the population occurring within a month of the lesions. This level of neuronal loss was then sustained for the remainder of the range of recovery times, up to >3 years post-lesion. In comparison, shrinkage of the LGN progressed more gradually, not reaching a stable value until 6 months post lesion. We also determined the time course of the expression of the calcium-binding protein calbindin (CB) in magnocellular (M) and parvocellular (P) layer neurons, a recently described form of neurochemical plasticity triggered by V1 lesions. We found that CB expression could be detected in surviving M and P neurons as early as 1 month after a lesion, with the percentage of neurons showing this neurochemical phenotype showing subtle changes over 6 months. Our study shows that there is a limited time window for any possible interventions aimed at reducing secondary neuronal loss in the visual afferent pathways following damage to V1.

neuroscience↗

bioRxiv2023

Wnt/β-catenin signaling controls mouse eyelid growth by mediating epithelial-mesenchymal interactions

Eyelid closure is required for the development of multiple ocular tissues. Interactions between the epithelium and underlying mesenchyme play a pivotal role in regulating eyelid development. However, the molecular mechanisms underlying these interactions remain unclear. Wnt signaling pathways regulate the development of ocular tissues, but their functions in eyelid development are not fully defined. In this study, we find that deletion of {beta}-catenin in supraorbital mesenchyme abolishes eyelid growth by causing decreased proliferation in supraorbital epithelium and underlying mesenchyme. Inhibition of Wnt secretion by deleting Wls in supraorbital epithelium results in failure of eyelid developing, similar to the effects of deleting mesenchymal {beta}-catenin, suggesting that mesenchymal Wnt/{beta}- catenin signaling is controlled by epithelial Wnt ligands during eyelid development. We also found that deletion of p63 results in formation of hypoplastic eyelids and reduced expression of several Wnt ligands in eyelid epithelium, indicating that expression of Wnt ligands in eyelid development is at least partially regulated by p63. Taken together, our data indicate that Wnt/{beta}-catenin signaling controls eyelid growth by orchestrating epithelial- mesenchymal interactions.

developmental biology↗

bioRxiv2023

Individual Variability in Structural Connectivity Architecture of the Human Brain across the Middle-aged and Old Adult

The human brain shows higher variability in functional connectivity in the heteromodal association cortex but lower variability in the unimodal cortex. As the anatomical substrate of functional connectivity, the temporal-spatial pattern of individual variability in structural connectivity remains largely unknown. In the present study, we depicted the temporal-spatial pattern of individual variability in structural connectivity, which is highest in the limbic regions and lowest in the unimodal sensorimotor regions. With increasing age, the variability in structural connectivity increased. Our results demonstrated that this specific spatial distribution relates to the plasticity of synapses and white matter. We proposed a modified ridge regression model to predict cognition individually and generate idiographic brain mapping. Individual variability in structural connectivity is significantly correlated with idiographic brain mapping. Overall, our study has potential implications for understanding biological and genetic mechanisms of variability in structural connectivity, guiding interventions to promote successful cognitive ageing and interpreting statistical maps in the human connectome.

neuroscience↗

bioRxiv2022

Modulating the epigenetic state promotes the reprogramming of transformed cells to pluripotency in a line-specific manner

Somatic cell reprogramming and oncogenic transformation share surprisingly similar features, yet transformed cells are highly resistant to reprogramming. There must be barriers that block transformed cells from reprogramming, but the nature of those barriers is unclear. In this study, we generated a systematic panel of transformed mouse embryonic fibroblasts (MEFs) using a variety of oncogenic transgenes, and discovered transformed cell lines that remain compatible with reprogramming when transfected with Oct4/Sox2/Klf4/Myc. By comparing the reprogramming-capable and incapable transformed lines we identified multiple stages of failure in the reprogramming process. Some transformed lines failed very early, whilst other lines seemed to progress through a normal-looking reprogramming process. Finally, we show that MEK inhibition overcomes one critical reprogramming barrier by indirectly suppressing a hyperactive epigenetic state in some of the transformed cells. This study reveals that the barriers underlying resistance to reprogramming vary between the different transformation methods. Key findingsO_LISomatic cell reprogramming of transformed cells is context-specific C_LIO_LIInhibition of MEK converts some cell lines to reprogramming-capable C_LIO_LITransformed cell lines are characterized by a hyperactive chromatin state C_LIO_LIMEK inhibition indirectly affects chromatin to enable reprogramming C_LI

cell biology↗

bioRxiv2022

Activation of innate immune cGAS-STING pathway contributes to Alzheimer pathogenesis in 5xFAD mice

cGAS senses microbial and host-derived double-stranded DNA (dsDNA) in cytoplasm to trigger cellular innate immune response in a STING-dependent manner. However, it remains unknown whether the cGAS-STING pathway in innate immunity contributes to Alzheimers disease (AD). Here we demonstrated the detectable binding of the cGAS-dsDNA in cytoplasm and the activation of microglial cGAS-STING pathway in brains of human AD and aged mice, suggesting a role for the cGAS-STING pathway in this neurodegenerative disease. Cgas-/-;5xFAD mice were largely protected from cognitive impairment, amyloid-{beta} (A{beta}) pathology, neuroinflammation and other sequelae associated with AD. Furthermore, Cgas deficiency in microglia inhibited the conversion of astrocytes into neurotoxic A1 phenotype, and thus alleviated oligomeric A{beta} peptides-induced neuronal toxicity. Finally, administration of STING inhibitor H-151 potently suppressed the activation of the cGAS-STING pathway and ameliorated AD pathogenesis in 5xFAD mouse model. In conclusion, our present study has identified a critical molecular link between innate immunity and AD, and suggests that therapeutic targeting of the cGAS-STING pathway activity might effectively interfere with the progression of AD.

neuroscience↗

bioRxiv2022

Phosphatidylserine controls synaptic targeting and membrane stability of ASIC1a

Phospholipid-protein interaction is highly specialized at the membranous nanodomains and critical for membrane receptor signaling. Calcium-permeable acid-sensing ion channel isoform 1a (ASIC1a) is a major neuronal proton sensor that contributes to synaptic plasticity. The functional outcome of ASIC1a is dependent on its surface targeting in synaptic subdomains; however, the lipid environment for ASIC1a and its role in channel targeting remain poorly understood. Here, we report that anionic phosphatidylserine (PS) is enriched in dendritic spines during neurodevelopment and it directly binds to ASIC1a through an electrostatic interaction with a di-arginine motif at ASIC1a C-terminus. PS regulates the membrane targeting and function of ASIC1a, which are both strongly suppressed by inhibition of PS synthesis. In cortical neuron dendrites, both PS and ASIC1a are predominately localized to peri-synaptic sites of spine heads, surrounding instead of overlapping with postsynaptic markers, PSD-95 and GluN1. Uncoupling the interaction between PS and ASIC1a by changing the charges to neutral or acidic at the di-arginine PS-binding motif, or applying a membrane penetrating competing peptide, caused mistargeting of ASIC1a at the synaptic sites, an overall increase in internalization and/or cytoplasmic accumulation of ASIC1a, and a decrease in its channel function. Together, our results provide novel insights on lipid microenvironment that governs ASIC1a expression and function at the membrane surface, especially peri-synaptic regions of dendritic spines, through an electrostatic interaction with anionic phospholipids.

neuroscience↗

bioRxiv2022

Transcriptome analysis of human preimplantation embryo reveals expressed waves associated with blastulation failure based on embryonic grade and age

In the in vitro fertilization and embryo transfer (IVF-ET) treatments, blastocyst culture is the method of choice for the generation of the embryos. Blastocysts can present different growth, quality, availability, and morphological characteristics that can be used to evaluate them. Although extreme blastocyst formation failures have been associated with the alteration of a single gene, the molecular factors responsible for arrested embryos remain unknown. RNA-sequencing (RNA-seq) is a promising tool for facilitating transcriptomic studies in early human embryos, thus allowing the investigation of gene expression discrepancies associated with different morphological criteria. Herein, we performed transcriptome analyses of the different stages of arrested human embryos. We identified candidate genes and related cell signaling pathways potentially associated with either arrested or developed embryos. Specifically, the three genes (MOV10L1, DDX4, and FKBP6) related to both DNA methylation and piRNA metabolic pathway might be involved in embryo development. Additionally, the transcriptome of arrested early blastocysts was significantly different from developed late blastocysts. Although the gene expression profiles identified were not significantly different between low- and high-quality late blastocysts, a significant difference in the profiles of day 5 and day 6 available late blastocysts was observed, which may be related to the clinical pregnancy rate associated with IVF-ET. Furthermore, we show that some chimeric RNAs may be functional in blastocyst development. Our findings uncovered new molecular markers that can be used for embryonic development detection, which might act as a tool for blastocyst selection for subsequent transfer.

genomics↗

bioRxiv2022

Connexin 43-mediated Neurovascular Interactions Regulate Neurogenesis in the Adult Brain Subventricular Zone

The subventricular zone (SVZ) is the largest neural stem cell (NSC) niche in the adult brain; herein, the blood-brain barrier is leaky, allowing direct interactions between NSCs and endothelial cells (ECs). Mechanisms by which direct NSC-EC interactions in the SVZ control NSC behavior are unclear. We found Cx43 to be highly expressed by both NSCs and ECs in the SVZ, and its deletion in either cell type leads to increased NSC proliferation and neuroblast generation, suggesting that Cx43-mediated NSC-EC interactions maintain NSC quiescence. This is further supported by in vitro studies showing co-culture with ECs decreases NSC proliferation and increases their expression of genes associated with quiescence in a Cx43-dependent manner. Cx43 mediates these effects in a channel-independent manner involving its cytoplasmic tail and ERK activation. Such insights further advance our understanding of NSC regulation in vivo and may inform NSC maintenance ex vivo for stem cell therapies for neurodegenerative disorders.

neuroscience↗

bioRxiv2022

The influence of leaf anatomical traits on photosynthetic in coffee leaves in Yunnan of China

Leaf photosynthesis is largely determined by anatomical features. This study aimed to reveal the quantitative effects of the anatomical structure of Coffea arabica leaves on photosynthesis. Pearsons correlation and path analysis were used to explore the correlation between leaf structure and photosynthesis. To calculate the comprehensive evaluation value of the correlation between leaf anatomical traits and photosynthetic parameters, the Criteria Importance Through Intercriteria Correlation (CRITIC) method was used to obtain the objective weight of each photosynthetic parameter. Most of the anatomical traits of the leaf significantly (P<0.05) to highly significantly (P<0.01) correlated with photosynthetic parameters, suggesting that anatomical traits greatly affected the photosynthetic capacity in Coffea arabica leaf. Likewise, path coefficient analysis revealed that the photosynthetic capacity of Arabic coffee leaves is strongly correlated, both directly and indirectly, with the stomatal characteristics of the leaves. The results of the comprehensive evaluation also indicated that leaf thickness (LT) and stomatal density (d) were the anatomical characteristics most closely related to photosynthesis. In these results, understanding the effects of the anatomical structure of coffee leaves on photosynthesis, may provide useful information for coffee breeding programs and the management of coffee plantations to increase photosynthesis.

biophysics↗

bioRxiv2022

Single-Objective Evanescent Scattering Microscopy for Imaging Single Proteins and Binding Kinetics

Plasmonic scattering microscopy has advanced the evanescent detection approaches by offering wide-field single-molecule imaging capability. However, two limitations prevent the broader application of plasmonic single-molecule imaging. One is the heating effect accompanying the plasmonic enhancement, and the other is the complicated system structure resulting from the two-objective optical arrangement. Here, we report single-objective evanescent scattering microscopy. The evanescent field is created by total internal reflection instead of the surface plasmon resonance on the gold film. As a result, the sensing substrate without gold film produces little heat, and allows excitation and observation using one objective. In addition, this system enables quantification of protein binding kinetics by simultaneously counting the binding of individual molecules and recording their binding sites with nanometer precision, providing a digital method to measure binding kinetics with high spatiotemporal resolution. This work may pave a road for label-free single protein analysis in conventional microscopy. TeaserLabel-free single-molecule imaging on a total internal reflection fluorescence objective.

biophysics↗

bioRxiv2021

Human embryos arrest in a quiescent-like state characterized by metabolic and zygotic genome activation problems

Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3-8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a quiescent-like state, marked by cell cycle arrest, the downregulation of ribosomes and histones and downregulation of MYC and p53 activity. Mechanistically, the arrested embryos can be divided into three types. Type I embryos fail to complete the maternal-zygotic transition, and type II/III embryos have erroneously low levels of glycolysis and variable levels of oxidative phosphorylation. Treatment with resveratrol or nicotinamide riboside (NR) can partially rescue the arrested phenotype. The mechanism of reactivation involves the upregulation of SIRT1, and activation of glycolysis and fatty acid oxidation which forces the embryos out of a quiescent state. Overall, our data reveal how human embryo arrest can be overcome by modulating metabolic pathways.

developmental biology↗

bioRxiv2021

CsMYB4a from Camellia sinensis Regulates the Auxin Signaling Pathway by Interacting with CsIAA4

Members of the R2R3-MYB4 subgroup are well-known negative regulatory transcription factors of phenylpropane and lignin pathways. In this study, we found that transgenic tobacco plants overexpressing a R2R3-MYB4 subgroup gene from Camellia sinensis (CsMYB4a) showed inhibited growth that was not regulated by phenylpropane and lignin pathways, and these plants exhibited altered sensitivity to synthetic auxin 1-naphthaleneacetic acid (-NAA) treatment. An auxin/indole-3-acetic acid 4 (AUX/IAA4) gene from Camellia sinensis (CsIAA4) participating in the regulation of the auxin signal transduction pathway was screened from the yeast two-hybrid library with CsMYB4a as the bait protein, and tobacco plants overexpressing this gene showed a series of auxin-deficiency phenotypes, such as dwarfism, small leaves, reduced lateral roots, and a shorter primary root. CsIAA4 transgenic tobacco plants were less sensitive to exogenous -NAA than control plants, which was consistent with the findings for CsMYB4a transgenic tobacco plants. The knockout of the endogenous NtIAA4 gene (a CsIAA4 homologous gene) in tobacco plants alleviated growth inhibition in CsMYB4a transgenic tobacco plants. Furthermore, protein-protein interaction experiments proved that domain II of CsIAA4 is the key motif for the interaction between CsIAA4 and CsMYB4a and that the degradation of CsIAA4 is prevented when CsMYB4a interacts with CsIAA4. In summary, our results suggest that CsMYB4a is a multifunctional transcription factor that regulates the auxin signaling pathway, phenylpropane and lignin pathways. This study provides new insights into the multiple functions of R2R3-MYB4 subgroup members as a group of well-known negative regulatory transcription factors. One-sentence summaryCsMYB4a act as multifunctional transcription factor that regulates the auxin signaling pathway, phenylpropane and lignin pathways.

physiology↗

bioRxiv2021

Keap1 recognizes EIAV early accessory protein Rev to promote antiviral defense

The Nrf2/Keap1 axis plays a complex role in viral susceptibility, virus-associated inflammation and immune regulation. However, whether or how the Nrf2/Keap1 axis is involved in the interactions between equine lentiviruses and their hosts remains unclear. Here, we demonstrate that the Nrf2/Keap1 axis was activated during EIAV infection. Mechanistically, EIAV-Rev competitively binds to Keap1 and releases Nrf2 from Keap1-mediated repression, leading to the accumulation of Nrf2 in the nucleus and promoting Nrf2 responsive genes transcription. Subsequently, we demonstrated that the Nrf2/Keap1 axis represses EIAV replication via two independent molecular mechanisms: directly increasing antioxidant enzymes to promote effective cellular resistance against EIAV infection, and repression of Rev-mediated RNA transport through direct interaction between Keap1 and Rev. Together, these data suggest that activation of the Nrf2/Keap1 axis mediates a passive defensive response to combat EIAV infection. The Nrf2/Keap1 axis could be a potential target for developing the strategies for combating EIAV infection. Author summaryHere we report that the Nrf2/Keap1 axis acts as an antiviral effector on EIAV replication through two-way regulation of Rev. On the one hand, EIAV-Rev activates the Nrf2/Keap1 axis by competitive interaction with Keap1, which promotes the transcription of cytoprotective genes implicated in the antiviral response. On the other hand, Keap1 restricts Rev/RRE-dependent RNA transport, leading to inhibition of viral protein synthesis and reduction in viral replication. This study highlights the importance of the Nrf2/Keap1 axis in controlling EIAV replication, and identifies this pathway as a potential new entry-point for treating lentivirus infection. Importantly, this report provides new insights into the regulation of viral replication by the Nrf2/Keap1 axis.

microbiology↗

bioRxiv2021

Systematic Chromosome Rearrangement Induced by CRISPR-Cas9 Reshapes the Genome and Transcriptome of Human Cells

Chromosome rearrangement plays important roles in development, carcinogenesis and evolution. However, its mechanism and subsequent effects are not fully understood. At present, large-scale chromosome rearrangement has been performed in the simple eukaryote, wine yeast, but the relative research in mammalian cells remains at the level of individual chromosome rearrangement due to technical limitations. In this study, we used CRISPR-Cas9 to target the highly repetitive human endogenous retrotransposons, LINE-1 (L1) and Alu, resulting in a large number of DNA double-strand breaks in the chromosomes. While this operation killed the majority of the cells, we eventually obtained live cell groups. Karyotype analysis and genome re-sequencing proved that we have achieved systematic chromosome rearrangement (SCR) in human cells. The copy number variations (CNVs) of the SCR genomes showed typical patterns that observed in tumor genomes. For example, the most frequent deleted region Chr9p21 containing p15 and p16 tumor suppressor, and the amplified region Chr8q24 containing MYC in tumors were all identified in both SCR cells. The ATAC-seq and RNA-seq further revealed that the epigenetic and transcriptomic landscapes were deeply reshaped by the SCR. Gene expressions related to p53 pathway, DNA repair, cell cycle and apoptosis were greatly altered to facilitate the cell survival under the severe stress induced by the large-scale chromosomal breaks. In addition, we found that the cells acquired CRISPR-Cas9 resistance after SCR by interfering with the Cas9 mRNA. Our study provided a new application of CRISPR-Cas9 and a practical approach for SCR in complex mammalian genomes. HighlightsRepetitive retroelements with large copy numbers were targeted using CRISPR-Cas9 in human cells. Cells survived after their chromosomal DNAs were heavily cleaved and systematic chromosome rearrangement was achieved. Systematic chromosome rearrangement reshaped the genome and transcriptome of the cells.

genomics↗

bioRxiv2021

Three-dimensional tracking of tethered particles for probing nanometer-scale single-molecule dynamics using plasmonic microscope

Three-dimensional (3D) tracking of surface-tethered single-particle reveals the dynamics of the molecular tether. However, most 3D tracking techniques lack precision, especially in axial direction, for measuring the dynamics of biomolecules with spatial scale of several nanometers. Here we present a plasmonic imaging technique that can track the motion of [~]100 tethered particles in 3D simultaneously with sub-nanometer axial precision at millisecond time resolution. By tracking the 3D coordinates of tethered particle with high spatial resolution, we are able to determine the dynamics of single short DNA and study its interaction with enzyme. We further show that the particle motion pattern can be used to identify specific and non-specific interactions in immunoassays. We anticipate that our 3D tracking technique can contribute to the understanding of molecular dynamics and interactions at the single-molecule level.

biophysics↗