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Techniques to Induce and Quantify Cellular Senescence
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Holotomography-Based, Label-Free Quantification of Cellular Dry Mass as a Biophysical Indicator of Microglial Aβ

Sunjeet Saha1, Amarnath Singam1, Melanie White1

  • 1University of Nevada, Las Vegas.

Research Square
|February 12, 2026
PubMed

Insights

Cellular dry mass measured by holotomography is a sensitive indicator of microglial senescence and impaired amyloid-beta phagocytosis, offering new biophysical insights into neurodegenerative disease progression.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biophysics

Background:

  • Senescent microglia exhibit altered molecular profiles and reduced amyloid-beta (Aβ) phagocytosis, contributing to neurodegenerative diseases.
  • Limited quantitative biophysical metrics exist to assess microglial dysfunction and its role in disease.

Purpose of the Study:

  • To identify sensitive biophysical indicators of microglial senescence and phagocytic capacity.
  • To establish cellular dry mass and morphology as markers for microglial dysfunction.

Main Methods:

  • Microglial senescence was induced using hydrogen peroxide (H₂O₂) and validated via p21/pRPS6 expression and Raman spectroscopy.
  • Label-free holotomography was used to measure cellular dry mass and morphological features.
  • Phagocytosis assays were performed after Aβ treatment.

Main Results:

  • Cellular dry mass strongly correlated with phagocytic decline in senescent microglia.
  • Senescent microglia treated with Aβ showed decreased dry mass and cell size, with enlarged nuclei, compared to controls.
  • Holotomography-derived dry mass serves as a robust, non-invasive indicator.

Conclusions:

  • Cellular dry mass is a sensitive biophysical marker for microglial senescence.
  • Dry mass and morphological changes reflect impaired Aβ phagocytosis in senescent microglia.
  • This approach offers a novel method for assessing microglial function in neurodegeneration.
Keywords:
amyloid-β (Aβ)dry massholotomographymicroglial cellphagocytosissenescence

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