Mechanical properties of glial cells

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Johns Hopkins University
In recent years, traumatic brain injury (TBI) has received an increase in attention as an “invisible wound”–where mild injuries are difficult to detect non-invasively and remain undiagnosed until postmortem analysis. As most of our knowledge comes from neuropathological evaluation of cellular damage, there is a need for relating the injurious loading to damage at the level of cellular networks. For example, recent analysis of postmortem samples from former football athletes, as well as military personnel, show peculiar damage surrounding arterioles–the small vessels of the arterial vasculature that feed into the capillary bed of the brain. The locations and extent of damage are largely dependent on heterogeneity of brain tissue, which at the length scale of interest ( 1-100 microns), is poorly defined. Glial cells–which encompass astrocytes, oligodendrocytes, and microglia–are con- ventionally believed to comprise the softer “isotropic matrix” which surround axons in previous multiscale models. However, heterogeneity at smaller length scales implies that this might no longer be the case, as the brain appears more as a fibrous network. To simplify the extremely dense and complex structure of brain tissue at the mesoscale, we aim to answer the question, Is there a length scale at which brain tissue constituents have homogeneous mechanical properties? To obtain local mechanical properties of glial cell processes, conventional techniques for obtaining cellular mechanical properties are mostly limited to probing cells grown on 2D substrates, which are shown to provide an unrealistic morphology for glial cells. In order to obtain mechanical properties of glial cell processes with a realistic morphologies, we devised a new experimental platform to probe cellular processes grown in a 3D polymeric scaffold via indentation by optically trapped silica beads. Due to the soft nature of glial cell processes, small forces can generate significantly large deformations–often exceeding the linear elastic regime described by classical Hertzian contact. In light of this observation, we developed a force-displacement relationship for the elliptical contact loading on a hyperelastic cylindrical body. Through our experiments, we demonstrate the glial cells have some mechanical properties that are predominantly homogeneous at small length scales, although their behavior is largely affected by strain-rate. Our findings provide a contribution to our understanding of mesoscale material properties of brain tissue. In the future, we hope this will aid in the development of accurate relationships between the mechanics and neuropathological observations following TBI.
biomechanics, cell mechanics, traumatic brain injury, optical trapping, hyperelasticity, indentation techniques