Abstract 5228: The impact of microtubules on solution conductance and capacitance; implications for the use of AC electric fields in cancer therapy
Notice bibliographique
Résumé
Abstract Microtubules (MTs) form mitotic spindles in dividing cells but have also been implicated in electrical signaling in biology, and may act as biological nanowires. Importantly, relatively weak AC electric fields with frequencies between 100-300 kHz and strengths in the range ~1-2.5 V/cm, called Tumor Treating Fields (TTFields), have been shown to arrest cancer cells’ mitosis and have led to an FDA approved treatment of glioblastoma multiforme. TTFields’ effect on MTs has motivated our study of their electrical properties. Here, we designed two platinum electrodes 14 μm apart and performed electrical characterization of solutions with various concentrations of MTs, tubulin dimers and ions, at a range of AC frequencies between 1 kHz and 1 MHz to uncover an optimal protocol to quantify MT electrical effects in vitro. We generated a theoretical basis for the results observed, by analyzing the response of ions as the principal charge carriers attracted to MTs and tubulin. We observed that MTs measurably increase the solution’s conductance, and this effect is more pronounced at lower ionic concentrations. We model the possibility that this effect is due to a larger percentage of ions being able to use MTs as low-resistance cables. The intrinsic conductivity of MTs has been found to be two orders of magnitude greater than that of the buffer solution. Moreover, we found that at 100 kHz the conductance of MTs reaches its peak. On the other hand, at low protein concentration, free tubulin dimers decrease solution’s conductance, and we model this as being due to tubulin attracting ionic charges and lowering their mobility. Both tubulin and MTs were found to increase capacitance of buffer solutions, due to their formation of ionic double layers. These results point to MTs being very sensitive to AC electric fields and further support their electrical signaling, an emerging property in biological organization. Modulating electrical signaling via 100kHz fields may impact intra-cellular communication as well as organization of the cytoskeleton. These results bring insight into MTs ability to modulate the capacitance and conductance of the cytoplasm and act as low resistance pathways for ions, which has implications for understanding of the action of TTFields on cancer cells. Citation Format: Jack A. Tuszynski, Iara Santelices, Douglas E. Friesen, Clayton Bell, Jack Xiao, Vahid Rezania, Holly Freedman, Cameron Hough, Andrew J. Tsung, Kiran K. Velpula, Karthik Shankar. The impact of microtubules on solution conductance and capacitance; implications for the use of AC electric fields in cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5228. doi:10.1158/1538-7445.AM2017-5228
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».