Spatial Organization of Biological Fuctions | BPS Thematic Meeting

Spatial Organization of Biological Functions Meeting

Poster Abstracts

22-POS Board 22 THE DYNAMICS OF INTRACELLULAR CHARGED SPECIES ON TTFIELD EXPOSURE Prerna Verma 1 ; Aarat Kalra 1 ; 1 Indian Institute of Technology, Delhi, Centre for Biomedical Engineering, Delhi, India Tumor Treating Fields (TTFields) employ low-intensity (2 V/cm), intermediate-frequency (100– 300 kHz) alternating electric fields as a non-invasive treatment modality for the treatment of several cancers, including glioblastoma and mesothelioma. Although the various intracellular consequences of TTField exposure are well reported, the biophysical mechanisms leading up to them are unclear. Here, we computationally investigate how TTFields influence the translational movement of proteins and ions. To identify the proteins and ions with the highest translational motion in response to TTFields, we developed a cost function based on mass, charge, and hydrodynamic radius and examined its value for all non-membrane and non-nuclear human proteins listed in the Protein Data Bank (PDB). We found 7OX6 (human interleukin-9), 6HPI (interleukin-36 alpha), 4YDX (human copper chaperone), 2LJK (human signaling protein), and 2RNB (human copper chaperone) to be the most responsive proteins. Hydroxide (OH-), potassium (K+), chloride (Cl-), acetate (CH3COO-), and sodium (Na+) were the most responsive ions. To mimic the physiological conditions in glioblastoma tumors, we developed a computational model of a cancer cell with radius of 5 µm embedded in gray matter, incorporating additional anatomical layers such as the scalp, skull, cerebrospinal fluid and white matter. Upon TTField exposure for 100 µs, the average movement of the most responsive human interleukin- 9 protein was approximately 4 µm, while that of sodium (Na⁺) ions was ab out 0.2 µm. Our findings show that the translational movement of proteins and ions is indeed influenced by TTFields, providing a viable biophysical explanation for downstream intracellular symptoms. Our work suggests that disruption of the translational movement of intracellular charged species play a key role in TTField-based cancer treatment.

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