CNS Cell Distribution and Axon Orientation Determine Local Spinal Cord Mechanical Properties

David E Koser,Emad Moeendarbary,Janina Hanne,Stefanie Kuerten,Kristian Franze

doi:10.1016/j.bpj.2015.03.039

David E Koser, Emad Moeendarbary + Show 3 more

Open Access

https://doi.org/10.1016/j.bpj.2015.03.039

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Abstract

Mechanical signaling plays an important role in cell physiology and pathology. Many cell types, including neurons and glial cells, respond to the mechanical properties of their environment. Yet, for spinal cord tissue, data on tissue stiffness are sparse. To investigate the regional and direction-dependent mechanical properties of spinal cord tissue at a spatial resolution relevant to individual cells, we conducted atomic force microscopy (AFM) indentation and tensile measurements on acutely isolated mouse spinal cord tissue sectioned along the three major anatomical planes, and correlated local mechanical properties with the underlying cellular structures. Stiffness maps revealed that gray matter is significantly stiffer than white matter irrespective of directionality (transverse, coronal, and sagittal planes) and force direction (compression or tension) (Kg= ∼130 Pa vs. Kw= ∼70 Pa); both matters stiffened with increasing strain. When all data were pooled for each plane, gray matter behaved like an isotropic material under compression; however, subregions of the gray matter were rather heterogeneous and anisotropic. For example, in sagittal sections the dorsal horn was significantly stiffer than the ventral horn. In contrast, white matter behaved transversely isotropic, with the elastic stiffness along the craniocaudal (i.e., longitudinal) axis being lower than perpendicular to it. The stiffness distributions we found under compression strongly correlated with the orientation of axons, the areas of cell nuclei, and cellular in plane proximity. Based on these morphological parameters, we developed a phenomenological model to estimate local mechanical properties of central nervous system (CNS) tissue. Our study may thus ultimately help predicting local tissue stiffness, and hence cell behavior in response to mechanical signaling under physiological and pathological conditions, purely based on histological data.

Highlights

The current textbook understanding of developmental and pathological processes in biological systems is mainly based on biochemical signaling
Gray matter is stiffer than white matter
In all three anatomical planes, gray matter was significantly stiffer than white matter at all tested indentation depths as well as for full indentation, i.e., at maximum force (N 1⁄4 5, n > 600, p < 10À76) (Fig. 3 A)

Summary

Introduction

The current textbook understanding of developmental and pathological processes in biological systems is mainly based on biochemical signaling. Even in the central nervous system (CNS), which is mechanically protected from external stresses by the surrounding meninges and bones (brain and spinal cord) or fibrous tissue (retina), cells adapt their morphology, proliferation, migration, and differentiation to the stiffness of their environment [7,8,9,10,11,12]. After introducing implants into the CNS, whose stiffness is orders of magnitude higher than that of the tissue, cells respond to the mechanical signals generated by the implant with an inflammatory reaction, culminating in a foreign body reaction [12]. Knowledge about the mechanical properties of CNS tissue at a length scale that is relevant to individual cells (approximately tens of micrometers) is currently sparse. Some CNS tissues were shown to be mechanically anisotropic, inhomogeneous, or to stiffen with strain, these studies were mostly done using different samples and methods, impeding comparability

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