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Cells Dynamically Adapt Their Nuclear Volumes and Proliferation Rates During Single to Multicellular Transitions.

Vaibhav Mahajan1, Keshav Gajendra Babu1, Markus Mukenhirn1,2

  • 1Dresden University of Technology, Biotechnology Center, Center for Molecular and Cellular Bioengineering, Dresden, Germany.

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Summary
This summary is machine-generated.

Cancer cell volume and mechanics change significantly when forming tumors. These biophysical shifts are linked to cell cycle adaptations, not just physical stress, impacting tumor development.

Keywords:
3D modelcell mechanicscell volumemulticellularityspheroidtumour microenvironment

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Area of Science:

  • Biophysics
  • Cell Biology
  • Cancer Research

Background:

  • Tumor development involves complex biophysical changes across multiple scales.
  • Cellular volume and mechanics regulation is crucial but poorly understood in dense tumor environments.

Purpose of the Study:

  • To investigate how cancer cell and nuclear volumes, mechanics, and cell cycle are regulated during multicellular transitions in tumors.
  • To determine the relationship between cell cycle adaptation and biophysical changes in developing tumor structures.

Main Methods:

  • Quantified cancer cell and nuclear volumes in multicellular spheroids within tunable hydrogels.
  • Assessed cell mechanical properties and cell cycle phase distribution.
  • Investigated the role of Cyclin-Dependent Kinase 1 (CDK1) inhibition.

Main Results:

  • Multicellular spheroid formation caused significant decreases in cell and nuclear volumes (up to 60% for nuclei).
  • These volume reductions were linked to cell cycle delays (G1-phase accumulation) and increased cell stiffness, not compressive stress.
  • Nuclear volume expanded and cells softened during multicellular-to-single cell transitions (invasion).

Conclusions:

  • Cellular and nuclear volumes, mechanics, and cell cycle progression are dynamically regulated by the multicellular state in tumors.
  • Cell cycle adaptation is a key driver of nuclear volume reduction in early tumor formation.
  • Understanding these biophysical regulations offers insights into tumor progression and invasion mechanisms.