Abstract

Positron annihilation lifetime spectroscopy (PALS) provides a direct measurement of the free volume void sizes in polymers and biological systems. This free volume is critical in explaining and understanding physical and mechanical properties of polymers. Moreover, PALS has been recently proposed as a potential tool in detecting cancer at early stages, probing the differences in the subnanometer scale free volume voids between cancerous/healthy skin samples of the same patient. Despite several investigations on free volume in complex cancerous tissues, no positron annihilation studies of living cancer cell cultures have been reported. We demonstrate that PALS can be applied to the study in human living 3D cell cultures. The technique is also capable to detect atomic scale changes in the size of the free volume voids due to the biological responses to TGF-β. PALS may be developed to characterize the effect of different culture conditions in the free volume voids of cells grown in vitro.

Highlights

  • Free volume voids play a key role in a variety of mechanical properties in polymers [1] and dynamic processes in biological systems, including permeability of small molecules and diffusion of drugs through cell membranes [2]

  • Our hypothesis is that biological responses to environmental factors, such as cellular differentiation and changes in cell colony structure are accompanied by atomic scale changes in the free volume void size of the cells, and that those changes can be characterized by Positron annihilation lifetime spectroscopy (PALS)

  • We show that PALS measurements are able to detect atomic scale changes of voids size in human colonic adenocarcinoma 3D cell cultures developing over time and when treated with transforming growth factor b (TGF-b)

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Summary

Introduction

Free volume voids play a key role in a variety of mechanical properties in polymers [1] and dynamic processes in biological systems, including permeability of small molecules and diffusion of drugs through cell membranes [2]. Our hypothesis is that biological responses to environmental factors, such as cellular differentiation and changes in cell colony structure are accompanied by atomic scale changes in the free volume void size of the cells, and that those changes can be characterized by PALS. To test this idea, we used a T84 human colon cancer 3D cell culture model under two different conditions that result in distinct in vitro multicellular organization of colonies. We show that PALS measurements are able to detect atomic scale changes of voids size in human colonic adenocarcinoma 3D cell cultures developing over time and when treated with TGF-b

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