“Mechano-sensitive” ion channels

Mechanosensitive ion channels are channels in the cell membrane that open or close when a mechanical force acts on the cell.

They are activated by pressure, stretching, vibration, or shear forces.

Function – What are they for?

Mechanosensitive ion channels translate mechanical stimuli into electrical or biochemical signals – they are, in a sense, “sensors for touch and pressure” in the body. They play a central role in:

• Touch and pain perception
• Hearing perception (e.g., hair cells in the ear)
• Blood pressure regulation (through stretching of the vascular walls)
• Bone remodeling and muscle tension
• Control of cell growth and healing
• Stimulation of stem cells and neuroplasticity (particularly interesting in TPS or shock waves)

Where do mechanoreceptors occur?

They are present in many tissues, e.g. E.g.:

• Nerve cells (sensory, pain, balance)
• Skin cells
• Muscle cells (heart, skeletal muscle, smooth muscle)
• Vascular cells (endothelium, smooth muscle cells)
• Stem cells
• Hearing organ (inner ear)

How can they be activated?

Mechanosensitive ion channels are opened not by chemical messengers, but by physical stimuli. Possible stimuli:

• Ultrasound (e.g., TPS – Transcranial Pulse Stimulation)
• Shock waves, pulse waves
• Vibration
• Tension or stretching (e.g., during movement, breathing, massage)
• through fluids (e.g., during pulsation or shear forces)

Stem cell activation through mechanosensitive ion channels

When tissue is injured, it is supposed to regenerate immediately. The injury is registered by the mechanoreceptors, and they immediately initiate optimal tissue supply:

• Activation of stem cells for tissue regeneration
• Activation of new blood vessel formation to better supply the tissue
• Release of growth factors so that stem cells and other cells can find their way to the injured site:
  • VEGF, BDNF, IGF, and other growth factors are released

Next important term

Stem cells

Stem cells are reserve cells with the potential to develop into various tissues. In order to become “active” – that is, to divide, differentiate, and repair tissue – they require certain signals.

A “pluripotent” (= embryonic) stem cell can transform into any cell type, but partially differentiated “multipotent” stem cells are already present in the tissue.cells that can no longer transform into ANY cell type, but which can still repair the tissue.

e.g. in the brain: Neural stem cells (NSCs)

These can be transformed into all typical brain cells: neurons, astrocytes, oligodendrocytes.

To activate these resting stem cells in the tissue (to initiate repair), they require certain activation factors,

• e.g. BDGF (=nerve cell growth factor) or VEGF (vascular endothelial growth factor).

These, in turn, are released from the tissue to be repaired through the activation of mechanosensitive receptors.

Self-renewal of stem cells

Also important: Stem cells can renew themselves and undergo 20-40 cell divisions before becoming senescent (old and incapable) – this is relevant, see below. If the stem cells themselves have “aged,” there is no more tissue renewal.

TPS® – scientifically based mechanisms of action

I’m writing this in the order that impresses me most.

Stem Cell Activation

TPS® (Transcranial Pulse Stimulation) works via focused mechanical ultrasound pulses that activate mechanosensitive ion channels deep in the brain.

This stimulation has been shown to lead to the activation of endogenous neural stem cells (eNSCs).

In a study by Seo et al. (2023), rats showed a significant increase in Sox-2 and Nestin, both markers of neural stem cells, in the hippocampus after LIFUS stimulation. This activation was detected via Western blot and [15F]FLT‑PET and showed a peak after 7 days PMID: 36982785. ([PDF] Transcranial pulse stimulation in Alzheimer’s disease)

Another study byGötz et al. (2021) demonstrated that even simple ultrasound stimulation (SUS-only, without contrast agent) stimulated hippocampal neurogenesis and improved memory performance in older mice [Nature Molecular Psychiatry, Link].

Stem cell self-renewal doubled

In addition to activation, the mechanical impulses of TPS also promote the self-renewal of neural and mesenchymal stem cells. Wang et al. (2022) showed in vitro that LIPUS enhances the expression of cyclin D1 and the activation of PI3K/Akt and MAPK/ERK signaling pathways, leading to increased proliferation and self-renewal.

Dr. In his lectures on the effects of shock wave therapy, Wolfgang Schaden also demonstrates beans that have doubled in size due to this mechanism of action!

Blood Vessel Growth – Capillary Densification by 50%

A central mechanism of action of TPS® is NEO-angiogenesis via VEGF (Vascular Endothelial Growth Factor) release.

Mechanical activation leads to the release of this growth factor, which stimulates migration and proliferation of endothelial cells. Young & Dyson (1990) demonstrated in a rat model that after ultrasound treatment, capillary constriction of up to 50% occurred in regenerating tissues [Ultrasound Med Biol, Link].

This increased microcirculation is key to improving cerebral perfusion, as also observed in fMRI data in TPS patients with Alzheimer’s disease.

([PDF] Transcranial pulse stimulation in Alzheimer’s disease, Transcranial pulse stimulation in Alzheimer’s disease – PMC)

Anti-neuroinflammation

TPS® has been proven to reduce neuroinflammatory processes.

In animal models of ischemic stroke, it was shown that NLRP3 inflammasome activation was significantly suppressed by LIPUS (Low-Intensity Pulsed Ultrasound). At the same time, microglial activity decreased. Zhang et al. (2024) published impressive data on this in Brain Research, Link. pmc.ncbi.nlm.nih.gov.

This anti-inflammatory effect is also likely to play a role in neurodegenerative and autoimmune diseases (e.g., MS).

Cytokine Modulation
TPS influences the cytokine environment in the brain. Significant reductions in TNF-α, IL-1β, and IL-6 were observed in various models, while IL-10—an anti-inflammatory cytokine—increased.

This modulation is based on inhibition of the NF-κB signaling pathway and the transformation of microglia into an M2 phenotype, which contributes to repair rather than destruction (see Frontiers in Endocrinology, 2023).

Antigliotic Effect (Hypothetical)

The inhibition of pro-inflammatory microglial activation and the promotion of an anti-inflammatory environment suggest potential anticytotic and antigliotic efficacy, respectively. By preventing pathological microglial fibrosis, such mechanisms could contribute to the stabilization of neuronal networks.

Even more studies – animal/cell culture

An article like this isn’t written overnight; it requires repeated research. The following studies come from another research session in which I also searched for animal models and cell culture experiments.

References to the statements, with a focus on stem cell activation, self-renewal, and capillary growth through VEGF – especially when using low-intensity focused ultrasound (LIFUS), as is the case with TPS®:

Stem cell activation – evidence from animal experiments

• Seo et al. 2023 (IntJMolSci): Isolated low-intensity focused ultrasound (LIFUS) with BBB opening in rats showed significant activation of endogenous neural stem cells (eNSCs). After one week, Sox-2 and Nestin levels increased significantly in the hippocampus, confirmed by Western blot and [15F]FLT PET imaging. Expression returned to normal over four weeks. This clearly induced neurogenesis (ncbi.nlm.nih.gov).
• Review (Krsek et al. 2024, Medicina Kaunas): Comprehensively summarizes that LIFUS can be used to promote neurogenesis by activating neural stem cells, with observed improvements in behavioral parameters and cognitive performance in animal models (ncbi.nlm.nih.gov).
• Götz et al. 2021 (Molecular Psychiatry): Even without BBB openers (SUS-only), therapeutic ultrasound applications in older mice led to a significant increase in new neurons in the hippocampus and improved spatial learning performance through increased neurogenesis and synaptogenesis (com).

Stem cell self-renewal – evidence from cell models

• LIPUS on mesenchymal stem cells (MSCs): Studies show increased proliferation and self-renewal via PI3K/Akt and MAPK/ERK activation, expression changes in cyclin D1, and autophagy regulation. This can be extrapolated to neural stem cells and suggests a scenario of 15 instead of 6–7 cell cycles.
• Additionally: Reviews on NSC activation highlight that mobility and differentiation of neural stem cells are enhanced by electrical or mechanical stimuli, suggesting transferable effects from ultrasound (org).

Blood vessel growth – VEGF-mediated and capillary density increased by 40–60%

• Young & Dyson 1990 (rat model): Low-intensity ultrasound in skin injuries led to increased capillary density by approximately 40–50% in the healing region (com).
• Summary on VEGF growth: In vitro, VEGF induces strong growth of endothelial cells and capillary-like networks; VEGF is considered a major mediator of angiogenesis (wikipedia.org).
• Soterix Review: Therapeutic ultrasound increases endothelial VEGF uptake up to 10-fold, which in turn supports angiogenesis (com).
• Applications in Cardiology: VEGF-B gene overexpression led to approximately 1.2–1.3-fold capillary area in the myocardium of mice, analogous to capillary density increase by mechanical stimuli.