Viscoelasticity and Volume of Cortical Neurons under Glutamate Excitotoxicity and Osmotic Challenges

Efremov, Yuri M.; Grebenik, Ekaterina A.; Sharipov, Rinat; Krasilnikova, Irina; Kotova, Svetlana; Акованцева, А. А.; Бакаева, З. В.; Pinelis, V. G.; Surin, Alexander; Timashev, Peter

doi:10.1016/j.bpj.2020.09.022

Cited by 14 publications

(9 citation statements)

References 55 publications

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“…By statistics, the average apparent heights of neurons treated with 0, 5, and 10 μM Aβ42 oligomers are 4.05 ± 0.54, 5.34 ± 0.47, and 5.78 ± 0.59 μm (Figure H). Compared to the control (0 μM), the heights of neurons treated by 5 and 10 μM Aβ42 oligomers are higher in significance, which is consistent with a previous study in which it was found that the soma’s height of cortical neurons increased about 10–30% upon treatment with glutamate of toxic concentrations . The above observations manifest that exposure to Aβ42 oligomers caused neuronal structural changes.…”

Section: Resultssupporting

confidence: 91%

“…Compared to the control (0 μM), the heights of neurons treated by 5 and 10 μM Aβ42 oligomers are higher in significance, which is consistent with a previous study in which it was found that the soma's height of cortical neurons increased about 10−30% upon treatment with glutamate of toxic concentrations. 43 The above observations manifest that exposure to Aβ42 oligomers caused neuronal structural changes. Since the shape/height of cells is mainly maintained by the cytoskeleton, 44 the results imply that Aβ42 oligomers induced cytoskeletal alterations of the neurons.…”

Section: Resultsmentioning

confidence: 79%

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Nanomechanical Profiling of Aβ42 Oligomer-Induced Biological Changes in Single Hippocampus Neurons

Tang

et al. 2023

ACS Nano

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Understanding how Aβ42 oligomers induce changes in neurons from a mechanobiological perspective has important implications in neuronal dysfunction relevant to neurodegenerative diseases. However, it remains challenging to profile the mechanical responses of neurons and correlate the mechanical signatures to the biological properties of neurons given the structural complexity of cells. Here, we quantitatively investigate the nanomechanical properties of primary hippocampus neurons upon exposure to Aβ42 oligomers at the single neuron level by using atomic force microscopy (AFM). We develop a method termed heterogeneity-load-unload nanomechanics (HLUN), which exploits the AFM force spectra in the whole loading–unloading cycle, allowing comprehensive profiling of the mechanical properties of living neurons. We extract four key nanomechanical parameters, including the apparent Young’s modulus, cell spring constant, normalized hysteresis, and adhesion work, that serve as the nanomechanical signatures of neurons treated with Aβ42 oligomers. These parameters are well-correlated with neuronal height increase, cortical actin filament strengthening, and calcium concentration elevation. Thus, we establish an HLUN method-based AFM nanomechanical analysis tool for single neuron study and build an effective correlation between the nanomechanical profile of the single neurons and the biological effects triggered by Aβ42 oligomers. Our finding provides useful information on the dysfunction of neurons from the mechanobiological perspective.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 79%

Nanomechanical Profiling of Aβ42 Oligomer-Induced Biological Changes in Single Hippocampus Neurons

Tang

et al. 2023

ACS Nano

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“…To this end, we measured the surface area of cells by tracking their fluorescence images and assuming that an increase in the area of fluorescent images of cells reflects an increase in their volume. Fluorescence images of Fura-FF loaded neurons were used to monitor changes in [Ca 2+ ]i and to track cell swelling, as described recently ( Efremov et al, 2020 ). The results obtained in two of the typical experiments employing the culture of cerebellar granular neurons are shown in Figure 5 .…”

Section: Resultsmentioning

confidence: 99%

“…First, LPS is capable not only of specifically interacting with transport proteins and protein complexes on the cell surface ( Kirk and Bazan, 2005 ; Sriram et al, 2015 ; Vijay, 2018 ), but, being an amphiphilic molecule with a significant hydrophobic moiety and a large hydrophilic region, LPS can also non-specifically bind to the plasma membrane, altering its properties ( Carr and Morrison, 1984 ; Casado and Ascher, 1998 ; Korinek et al, 2015 ). Second, change in the rheological properties of the cell plasma membrane can lead to the increase in cytosolic osmolarity and swelling of the neuronal soma ( Efremov et al, 2020 ), which is observed, for example, in cultured cortical neurons at glutamate administration due to the entry of the large amount of Ca 2+ and Na + via NMDA channels ( Kiedrowski, 1999 ; Sharipov et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…We have recently shown that toxic doses of glutamate cause rapid swelling of neurons and change the rheological properties of the plasma membrane ( Efremov et al, 2020 ). Fragments of LPS with a truncated hydrophilic part were able to alter the mechanical properties of the plasma membrane and modulate activity of the plasma membrane proteins ( Casado and Ascher, 1998 ; Korinek et al, 2015 ), accelerating or slowing toxin-induced cell lysis ( Carr and Morrison, 1984 ).…”

Section: Introductionmentioning

confidence: 99%

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Lipopolysaccharide From E. coli Increases Glutamate-Induced Disturbances of Calcium Homeostasis, the Functional State of Mitochondria, and the Death of Cultured Cortical Neurons

Бакаева

Lizunova

Tarzhanov

et al. 2022

Front. Mol. Neurosci.

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Lipopolysaccharide (LPS), a fragment of the bacterial cell wall, specifically interacting with protein complexes on the cell surface, can induce the production of pro-inflammatory and apoptotic signaling molecules, leading to the damage and death of brain cells. Similar effects have been noted in stroke and traumatic brain injury, when the leading factor of death is glutamate (Glu) excitotoxicity too. But being an amphiphilic molecule with a significant hydrophobic moiety and a large hydrophilic region, LPS can also non-specifically bind to the plasma membrane, altering its properties. In the present work, we studied the effect of LPS from Escherichia coli alone and in combination with the hyperstimulation of Glu-receptors on the functional state of mitochondria and Ca2+ homeostasis, oxygen consumption and the cell survival in primary cultures from the rats brain cerebellum and cortex. In both types of cultures, LPS (0.1–10 μg/ml) did not change the intracellular free Ca2+ concentration ([Ca2+]i) in resting neurons but slowed down the median of the decrease in [Ca2+]i on 14% and recovery of the mitochondrial potential (ΔΨm) after Glu removal. LPS did not affect the basal oxygen consumption rate (OCR) of cortical neurons; however, it did decrease the acute OCR during Glu and LPS coapplication. Evaluation of the cell culture survival using vital dyes and the MTT assay showed that LPS (10 μg/ml) and Glu (33 μM) reduced jointly and separately the proportion of live cortical neurons, but there was no synergism or additive action. LPS-effects was dependent on the type of culture, that may be related to both the properties of neurons and the different ratio between neurons and glial cells in cultures. The rapid manifestation of these effects may be the consequence of the direct effect of LPS on the rheological properties of the cell membrane.

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The cell softening as a universal indicator of cell damage during cytotoxic effects

Murashko

Frolova

Akovantseva

et al. 2023

Biochimica et Biophysica Acta (BBA) - General Subjects

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Viscoelasticity and Volume of Cortical Neurons under Glutamate Excitotoxicity and Osmotic Challenges

Cited by 14 publications

References 55 publications

Nanomechanical Profiling of Aβ42 Oligomer-Induced Biological Changes in Single Hippocampus Neurons

Nanomechanical Profiling of Aβ42 Oligomer-Induced Biological Changes in Single Hippocampus Neurons

Lipopolysaccharide From E. coli Increases Glutamate-Induced Disturbances of Calcium Homeostasis, the Functional State of Mitochondria, and the Death of Cultured Cortical Neurons

The cell softening as a universal indicator of cell damage during cytotoxic effects

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