Contact-Free Nuclear and Cytoplasmic Mechanophenotyping by Amplitude-Modulated Ultrasound and Phase-Locked Optical Diffraction Tomography: Computational Feasibility and Initial Experimental Readouts
Abstract
We investigate whether acoustic stimulation combined with phase-locked optical diffraction tomography (ODT) could measure the mechanical responses of the nucleus and cytoplasm separately in adherent cells. A megahertz ultrasound carrier is amplitude-modulated at low frequencies, while angle-scanned holography provides a route to reconstruct the first-harmonic refractive-index response in three dimensions. We built a computational model connecting viscoelastic finite-element simulations of MDA-MB-231 cells with a refractive-index phantom, hologram formation, camera noise and ODT reconstruction. Under an assumed 0.1 Pa harmonic shear traction at 10 Hz, the model predicts 3.6 to 9.2 nm of nuclear shear and 6.6 to 15.1 nm of apical motion. The nuclear-to-cytoplasmic amplitude ratio (R_A) is primarily sensitive to stiffness contrast in the tested scenarios, while the relative phase (Delta phi) responds to differences in dissipation. A simulated protocol using 100 illumination angles and 16 phase visits per angle recovered an imposed stiffening and recovery trajectory after averaging four acquisitions. We also obtained initial 3D tomograms of adherent MDA-MB-231 cells and report preliminary regional measurements from five cells. Their mean amplitude ratio was 0.616 plus or minus 0.098, and their mean relative phase was -1.91 plus or minus 0.58 degrees (mean and between-cell sample standard deviation). All five amplitude ratios were below unity, and all phase differences were negative, consistent with the qualitative directions of selected model scenarios. The small cohort and the absence of independently quantified experimental phase noise prevent a claim of quantitative mechanical validation. Together, these results support further evaluation of phase-locked acoustic ODT and identify experimental requirements for a controlled validation study.
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BibTeX
@misc{isik2026contactfree,
title = {{Contact-Free Nuclear and Cytoplasmic Mechanophenotyping by Amplitude-Modulated Ultrasound and Phase-Locked Optical Diffraction Tomography: Computational Feasibility and Initial Experimental Readouts}},
author = {Yagmur Isik and Merve Sevgi and Esmahan Caglar and Aysenur Akgun and Hasan Berkay Abdioglu and Gokhan Bora Esmer and Huseyin Uvet},
howpublished = {arXiv},
year = {2026},
month = oct,
doi = {10.48550/arxiv.2610.33369},
eprint = {2610.33369},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2610.33369},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - UNPB
TI - Contact-Free Nuclear and Cytoplasmic Mechanophenotyping by Amplitude-Modulated Ultrasound and Phase-Locked Optical Diffraction Tomography: Computational Feasibility and Initial Experimental Readouts
AU - Yagmur Isik
AU - Merve Sevgi
AU - Esmahan Caglar
AU - Aysenur Akgun
AU - Hasan Berkay Abdioglu
AU - Gokhan Bora Esmer
AU - Huseyin Uvet
PY - 2026
DA - 2026/10/23
PB - arXiv
DO - 10.48550/arxiv.2610.33369
UR - https://arxiv.org/abs/2610.33369
AB - We investigate whether acoustic stimulation combined with phase-locked optical diffraction tomography (ODT) could measure the mechanical responses of the nucleus and cytoplasm separately in adherent cells. A megahertz ultrasound carrier is amplitude-modulated at low frequencies, while angle-scanned holography provides a route to reconstruct the first-harmonic refractive-index response in three dimensions. We built a computational model connecting viscoelastic finite-element simulations of MDA-MB-231 cells with a refractive-index phantom, hologram formation, camera noise and ODT reconstruction. Under an assumed 0.1 Pa harmonic shear traction at 10 Hz, the model predicts 3.6 to 9.2 nm of nuclear shear and 6.6 to 15.1 nm of apical motion. The nuclear-to-cytoplasmic amplitude ratio (R_A) is primarily sensitive to stiffness contrast in the tested scenarios, while the relative phase (Delta phi) responds to differences in dissipation. A simulated protocol using 100 illumination angles and 16 phase visits per angle recovered an imposed stiffening and recovery trajectory after averaging four acquisitions. We also obtained initial 3D tomograms of adherent MDA-MB-231 cells and report preliminary regional measurements from five cells. Their mean amplitude ratio was 0.616 plus or minus 0.098, and their mean relative phase was -1.91 plus or minus 0.58 degrees (mean and between-cell sample standard deviation). All five amplitude ratios were below unity, and all phase differences were negative, consistent with the qualitative directions of selected model scenarios. The small cohort and the absence of independently quantified experimental phase noise prevent a claim of quantitative mechanical validation. Together, these results support further evaluation of phase-locked acoustic ODT and identify experimental requirements for a controlled validation study.
ER -