Ion-Based Cellular Signal Transmission, Principles of Minimum Information Loss, and Evolution by Natural Selection

The Extreme Physical Information EPI principle states that maximum information transmission or, equivalently, a minimum information loss is a fundamental property of nature. Prior work has demonstrated the universal EPI principle allows derivation of nearly all physical laws. Here, we investigate whether EPI can similarly give rise to the fundamental law of life: Evolution. Living systems require information to survive and proliferate. Heritable information in the genome encodes the structure and function of cellular macromolecules but this information remains fixed over time. In contrast, a cell must rapidly and continuously access, analyze, and respond to a wide range of continuously changing spatial and temporal information in the environment. We propose these two information dynamics are linked because the genes encode the structure of the macromolecules that form information conduits necessary for the dynamical interactions with the external environment. However, because the genome does not have the capacity to precisely locate the time and location of external signals, we propose the cell membrane is the site at which most external information is received and processed. In our model, an external signal is detected by gates on transmembrane ion channel and transmitted into the cytoplasm through ions that flow along pre-existing concentration gradients when the gate opens. The resulting cytoplasmic ion “puff” is localized in both time and space, thus producing spatial and temporal information. Small, localized signals in the cytoplasm are “processed” through alterations in the function and location of peripheral membrane proteins. Larger perturbations produce prolonged or spatially extensive changes in cytoplasmic ion concentrations that can be transmitted to other organelles via ion flows along elements of the cytoskeleton. An evolutionary constraint to the ever-increasing acquisition of environmental information is the cost of doing so. One solution to this trade-off is the evolution of information conduits that minimize signal loss during transmission. Since the structures of these conduits are encoded in the genome, evolution of macromolecular conduits that minimize signal loss is linked to and, in fact, governed by a universal principle, termed extreme physical information (EPI). Mathematical analysis of information dynamics based on the flow of ions through membrane channels and along wire-like cytoskeleton macromolecules fulfills the EPI principle. Thus, the empirically derived model of evolution by natural selection, although uniquely applicable to living systems, is theoretically grounded in a universal principle that can also be used to derive the laws of physics. Finally, if minimization of signal loss is a mechanism to overcome energy constraints, the model predicts increasing information and associated complexity are closely linked to increased efficiency of energy production or improved substrate acquisition.
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High Intensity Focused Ultrasound (HIFU) Triggers Immune Sensitization of Refractory Murine Neuroblastoma to Checkpoint Inhibitor Therapy.

Magnetic frequencies are not the only alternatives:

"Combining HIFU with αCTLA-4 and αPD-L1 significantly enhances anti-tumor response, improving survival from 0 to 62.5%.
HIFU alone causes upregulation of splenic and lymph node NK cells and circulating IL-2, IFN-Ɣ, and DAMPs, whereas immune regulators like CD4+Foxp3+, IL-10, and VEGF-A are significantly reduced.
HIFU combined with checkpoint inhibitors induced significant increases in intratumoral CD4+, CD8ɑ+, and CD8α+CD11c+ cells, CD11c+ in regional lymph nodes, and decrease in circulating IL-10 compared to untreated group.
We also report significant abscopal effect following unilateral treatment of mice with large, established bilateral tumors using HIFU and checkpoint inhibitors compared to tumors treated with HIFU or checkpoint inhibitors alone (61.1% survival, p<0.0001).
This combination treatment significantly also induces CD4+CD44+hiCD62L+low and, CD8α+CD44+hiCD62L+low population and are adoptively transferable imparting immunity, slowing subsequent de novo tumor engraftment."

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