Programmable Modulation for Extracellular Vesicles

Wang, Yihua; Melvin, R. A.; Bemis, Lynne T.; Worrell, Gregory A.; Wang, Hailong

doi:10.1101/566448

Cited by 14 publications

(6 citation statements)

References 41 publications

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“…4 D ). The observed distribution of the EV population underlines the heterogeneity of their secretion and reinforces the hypothesis that these subpopulations are secreted at different frequencies ( 29 ). Moreover, these results emphasize the need for several markers to adequately identify EVs or exosomes.…”

Section: Resultssupporting

confidence: 82%

Identifying extracellular vesicle populations from single cells

Nikoloff

Saucedo-Espinosa

Kling

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Extracellular vesicles (EVs) are constantly secreted from both eukaryotic and prokaryotic cells. EVs, including those referred to as exosomes, may have an impact on cell signaling and an incidence in diseased cells. In this manuscript, a platform to capture, quantify, and phenotypically classify the EVs secreted from single cells is introduced. Microfluidic chambers of about 300 pL are employed to trap and isolate individual cells. The EVs secreted within these chambers are then captured by surface-immobilized monoclonal antibodies (mAbs), irrespective of their intracellular origin. Immunostaining against both plasma membrane and cytosolic proteins was combined with highly sensitive, multicolor total internal reflection fluorescence microscopy to characterize the immobilized vesicles. The data analysis of high-resolution images allowed the assignment of each detected EV to one of 15 unique populations and demonstrated the presence of highly heterogeneous phenotypes even at the single-cell level. The analysis also revealed that each mAb isolates phenotypically different EVs and that more vesicles were effectively immobilized when CD63 was targeted instead of CD81. Finally, we demonstrate how a heterogeneous suppression in the secreted vesicles is obtained when the enzyme neutral sphingomyelinase is inhibited.

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Section: Resultssupporting

confidence: 82%

Identifying extracellular vesicle populations from single cells

Nikoloff

Saucedo-Espinosa

Kling

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…Similarly, SMEFs could play a role in inter-hemispheric communication, bypassing corpus callosum connections. Other recent work suggests that they could play a role in the modulation of release of extracellular vesicles [61], a newly discovered form of cellular communication.…”

Section: Discussionmentioning

confidence: 99%

Realistic modeling of mesoscopic ephaptic coupling in the human brain

Ruffini

Salvador²,

Tadayon

et al. 2020

PLoS Comput Biol

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Several decades of research suggest that weak electric fields may influence neural processing, including those induced by neuronal activity and proposed as a substrate for a potential new cellular communication system, i.e., ephaptic transmission. Here we aim to model mesoscopic ephaptic activity in the human brain and explore its trajectory during aging by characterizing the electric field generated by cortical dipoles using realistic finite element modeling. Extrapolating from electrophysiological measurements, we first observe that modeled endogenous field magnitudes are comparable to those in measurements of weak but functionally relevant self-generated fields and to those produced by noninvasive transcranial brain stimulation, and therefore possibly able to modulate neuronal activity. Then, to evaluate the role of these fields in the human cortex in large MRI databases, we adapt an interaction approximation that considers the relative orientation of neuron and field to estimate the membrane potential perturbation in pyramidal cells. We use this approximation to define a simplified metric (EMOD1) that weights dipole coupling as a function of distance and relative orientation between emitter and receiver and evaluate it in a sample of 401 realistic human brain models from healthy subjects aged 16-83. Results reveal that ephaptic coupling, in the simplified mesoscopic modeling approach used here, significantly decreases with age, with higher involvement of sensorimotor regions and medial brain structures. This study suggests that by providing the means for fast and direct interaction between neurons, ephaptic modulation may contribute to the complexity of human function for cognition and behavior, and its modification across the lifespan and in response to pathology.

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“…Besides the mobility of intracellular vesicles, gene expression in astrocytes can also be affected by the sleep-wake cycles (72). Previously, we reported a frequency-dependent effect of externally applied electrical stimulation on the secretion of astrocytic extracellular vesicles (EVs), including the profiles of EV size distribution, EV surface proteins, and EV-carrying microRNAs (73).…”

Section: Discussionmentioning

confidence: 99%

The frequency-dependent effect of electrical fields on the mobility of intracellular vesicles in astrocytes

Wang

Burghardt

Worrell

et al. 2020

Preprint

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Slow-wave sleep, defined by low frequency (<4 Hz) electrical brain activity, is a basic brain function affecting metabolite clearance and memory consolidation. Although the origin of lowfrequency activity is related to cortical up and down states, the underlying cellular mechanism of how low-frequency activity becomes effective has remained elusive. We applied electrical stimulation to cultured glial astrocytes while monitored the trafficking of GFP-tagged intracellular vesicles using TIRFM. We found a frequency-dependent effect of electrical stimulation that electrical stimulation in low frequency elevates the mobility of astrocytic intracellular vesicles. We suggest a novel mechanism of brain modulation that electrical signals in the lower range frequencies embedded in brainwaves modulate the functionality of astrocytes for brain homeostasis and memory consolidation. This finding suggests a physiological mechanism whereby endogenous low-frequency brain oscillations enhance astrocytic function that may underlie some of the benefits of slow-wave sleep and highlights possible medical device approach for treating neurological diseases.

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Programmable Modulation for Extracellular Vesicles

Cited by 14 publications

References 41 publications

Identifying extracellular vesicle populations from single cells

Identifying extracellular vesicle populations from single cells

Realistic modeling of mesoscopic ephaptic coupling in the human brain

The frequency-dependent effect of electrical fields on the mobility of intracellular vesicles in astrocytes

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