Ventral cytoskeletal remodeling as a mechanism for oscillatory load-induced Piezo1 overactivation and cancer cell vulnerability.
4 affiliations
- 1Faculty of Technology and Metallurgy, Department of Chemical Engineering, University of Belgrade, Belgrade, Serbia.
- 2School of Physics and Astronomy, Lancaster University, Lancaster, LA1 4YB UK.
- 3Mechanosensory Biophysics Laboratory, Victor Chang Cardiac Research Institute, Sydney, Australia.
- 4St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW Australia.
Abstract
The limited selectivity of conventional cancer therapies has stimulated interest in alternative approaches that exploit the distinct mechanical properties of cancer cells. Oscillatory mechanical stimuli, including low-intensity ultrasound and cyclic cellular deformation, represent promising non-chemical strategies capable of inducing selective cancer cell death through activation of the mechanosensitive ion channel Piezo1. However, the mechanisms linking external mechanical loading to Piezo1 overactivation remain insufficiently understood. This review presents a unified mechanobiological framework describing how frequency-dependent remodeling of the ventral cytoskeleton regulates Piezo1 activity in mesenchymal-like cancer cells. The heterogeneous and anisotropic organization of the cancer cell cytoskeleton enables specific mechanical responses, including stress localization, domain twisting under oscillatory extension, and domain tilting under ultrasound stimulation. These remodeling processes alter membrane-cytoskeleton coupling, focal adhesion-associated curvature formation, and Piezo1 conformational dynamics. In particular, torsional loading and curvature-dependent modulation of Piezo1 clusters provide potential mechanisms for sustained channel activation and Ca2⁺-mediated apoptosis. The proposed framework demonstrates that the response to oscillatory mechanical stimulation depends on the interplay between loading parameters and the dynamically remodeled mechanical state of the basal membrane-cytoskeleton system. These insights provide a physical basis for developing mechanically selective anticancer strategies by optimizing oscillatory stimuli to exploit cancer cell-specific vulnerabilities while preserving healthy tissues.
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BibTeX
@article{pajiclijakovic2026ventral,
title = {{Ventral cytoskeletal remodeling as a mechanism for oscillatory load-induced Piezo1 overactivation and cancer cell vulnerability.}},
author = {Ivana Pajic-Lijakovic and Milan Milivojevic and Boris Martinac and Peter V E McClintock},
journal = {Biophysical reviews},
year = {2026},
month = aug,
doi = {10.1007/s12551-026-01461-8},
url = {https://europepmc.org/article/MED/42927072},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ventral cytoskeletal remodeling as a mechanism for oscillatory load-induced Piezo1 overactivation and cancer cell vulnerability.
AU - Ivana Pajic-Lijakovic
AU - Milan Milivojevic
AU - Boris Martinac
AU - Peter V E McClintock
PY - 2026
DA - 2026/08/01
JO - Biophysical reviews
DO - 10.1007/s12551-026-01461-8
UR - https://europepmc.org/article/MED/42927072
AB - The limited selectivity of conventional cancer therapies has stimulated interest in alternative approaches that exploit the distinct mechanical properties of cancer cells. Oscillatory mechanical stimuli, including low-intensity ultrasound and cyclic cellular deformation, represent promising non-chemical strategies capable of inducing selective cancer cell death through activation of the mechanosensitive ion channel Piezo1. However, the mechanisms linking external mechanical loading to Piezo1 overactivation remain insufficiently understood. This review presents a unified mechanobiological framework describing how frequency-dependent remodeling of the ventral cytoskeleton regulates Piezo1 activity in mesenchymal-like cancer cells. The heterogeneous and anisotropic organization of the cancer cell cytoskeleton enables specific mechanical responses, including stress localization, domain twisting under oscillatory extension, and domain tilting under ultrasound stimulation. These remodeling processes alter membrane-cytoskeleton coupling, focal adhesion-associated curvature formation, and Piezo1 conformational dynamics. In particular, torsional loading and curvature-dependent modulation of Piezo1 clusters provide potential mechanisms for sustained channel activation and Ca2⁺-mediated apoptosis. The proposed framework demonstrates that the response to oscillatory mechanical stimulation depends on the interplay between loading parameters and the dynamically remodeled mechanical state of the basal membrane-cytoskeleton system. These insights provide a physical basis for developing mechanically selective anticancer strategies by optimizing oscillatory stimuli to exploit cancer cell-specific vulnerabilities while preserving healthy tissues.
SN - 1867-2450
SN - 1867-2469
ER -