Regional variations in stiffness in live mouse brain tissue determined by depth-controlled indentation mapping

Nelda Antonovaite,Davide Iannuzzi,Elly M Hol,Steven V Beekmans,Wytse J Wadman

doi:10.1038/s41598-018-31035-y

Abstract

The mechanical properties of brain tissue play a pivotal role in neurodevelopment and neurological disorders. Yet, at present, there is no consensus on how the different structural parts of the tissue contribute to its stiffness variations. Here, we have gathered depth-controlled indentation viscoelasticity maps of the hippocampus of acute horizontal live mouse brain slices. Our results confirm the highly viscoelestic nature of brain tissue. We further show that the mechanical properties are non-uniform and at least related to differences in morphological composition. Interestingly, areas with higher nuclear density appear to be softer than areas with lower nuclear density.

Highlights

Brain tissue consists of neuronal cell bodies, their processes, the interconnecting extracellular brain matrix (ECM), glial cells, blood vessels, and extracellular fluid
Atomic force microscope (AFM) indentation, on the contrary, makes use of a small radius tip to locally probe the mechanical response of a material to a compressive stress, and, seems to be more suitable to assess how the mechanical properties of the different regions of the brain may be influenced by the underlying morphological composition[43]
The size of the indentation sphere and the depth of indentation were selected to ensure that the measurements could provide the tissue mechanical features of the subregional area of the tested sample

Summary

Introduction

Brain tissue consists of neuronal cell bodies, their processes (dendrites and axons, myelinated or not, which form either sparse branches and arborizations or dense fiber bundles), the interconnecting extracellular brain matrix (ECM), glial cells, blood vessels, and extracellular fluid Each of these components as well as their joint organization may have a different influence on the local mechanical properties of the tissue, which, in turn, regulate a wide variety of very relevant mechanotransduction phenomena. The results reported in the literature do not always agree with each other, as witnessed by the wide range of stiffness values reported[39,42,44] Tantalized by this challenge, we have explored whether a recently introduced mechanical testing technique, known as ferrule-top dynamic indentation[45,46], could provide a better insight on the correlation between the composition of brain tissue and its viscoelastic properties. Calculating the mean measured stiffness of eleven anatomical subregions, and comparing it with the estimated nuclear densities, we can infer that densely packed cell layers may have lower stiffness than more disperse ones–a result that seems to contradict the commonly accepted assumption that brain tissue stiffness is dominated by cell bodies[3,30]

Methods

Results

Conclusion