All Publications


  • The mechanical importance of myelination in the central nervous system. Journal of the mechanical behavior of biomedical materials Weickenmeier, J., de Rooij, R., Budday, S., Ovaert, T. C., Kuhl, E. 2017

    Abstract

    Neurons in the central nervous system are surrounded and cross-linked by myelin, a fatty white substance that wraps around axons to create an electrically insulating layer. The electrical function of myelin is widely recognized; yet, its mechanical importance remains underestimated. Here we combined nanoindentation testing and histological staining to correlate brain stiffness to the degree of myelination in immature, pre-natal brains and mature, post-natal brains. We found that both gray and white matter tissue stiffened significantly (p≪0.001) upon maturation: the gray matter stiffness doubled from 0.31±0.20kPa pre-natally to 0.68±0.20kPa post-natally; the white matter stiffness tripled from 0.45±0.18kPa pre-natally to 1.33±0.64kPa post-natally. At the same time, the white matter myelin content increased significantly (p≪0.001) from 58±2% to 74±9%. White matter stiffness and myelin content were correlated with a Pearson correlation coefficient of ρ=0.92 (p≪0.001). Our study suggests that myelin is not only important to ensure smooth electrical signal propagation in neurons, but also to protect neurons against physical forces and provide a strong microstructural network that stiffens the white matter tissue as a whole. Our results suggest that brain tissue stiffness could serve as a biomarker for multiple sclerosis and other forms of demyelinating disorders. Understanding how tissue maturation translates into changes in mechanical properties and knowing the precise brain stiffness at different stages of life has important medical implications in development, aging, and neurodegeneration.

    View details for DOI 10.1016/j.jmbbm.2017.04.017

    View details for PubMedID 28462864

  • Modeling molecular mechanisms in the axon COMPUTATIONAL MECHANICS de Rooij, R., Miller, K. E., Kuhl, E. 2017; 59 (3): 523-537
  • Brain stiffness increases with myelin content. Acta biomaterialia Weickenmeier, J., de Rooij, R., Budday, S., Steinmann, P., Ovaert, T. C., Kuhl, E. 2016; 42: 265-272

    Abstract

    Brain stiffness plays an important role in neuronal development and disease, but reported stiffness values vary significantly for different species, for different brains, and even for different regions within the same brain. Despite extensive research throughout the past decade, the mechanistic origin of these stiffness variations remains elusive. Here we show that brain tissue stiffness is correlated to the underlying tissue microstructure and directly proportional to the local myelin content. In 116 indentation tests of six freshly harvested bovine brains, we found that the cerebral stiffnesses of 1.33±0.63kPa in white matter and 0.68±0.20kPa in gray matter were significantly different (p<0.01). Strikingly, while the inter-specimen variation was rather moderate, the minimum and maximum cerebral white matter stiffnesses of 0.59±0.19 kPa and 2.36±0.64kPa in each brain varied by a factor of four on average. To provide a mechanistic interpretation for this variation, we performed a histological characterization of the tested brain regions. We stained the samples with hematoxylin and eosin and luxol fast blue and quantified the local myelin content using image analysis. Interestingly, we found that the cerebral white matter stiffness increased with increasing myelin content, from 0.72kPa at a myelin content of 64-2.45kPa at a myelin content of 89%, with a Pearson correlation coefficient of ρ=0.91 (p<0.01). This direct correlation could have significant neurological implications. During development, our results could help explain why immature, incompletely myelinated brains are softer than mature, myelinated brains and more vulnerable to mechanical insult as evident, for example, in shaken baby syndrome. During demyelinating disease, our findings suggest to use stiffness alterations as clinical markers for demyelination to quantify the onset of disease progression, for example, in multiple sclerosis. Taken together, our study indicates that myelin might play a more important function than previously thought: It not only insulates signal propagation and improves electrical function of single axons, it also provides structural support and mechanical stiffness to the brain as a whole.Increasing evidence suggests that the mechanical environment of the brain plays an important role in neuronal development and disease. Reported stiffness values vary significantly, but the origin of these variations remains unknown. Here we show that stiffness of our brain is correlated to the underlying tissue microstructure and directly proportional to the local myelin content. Myelin has been discovered in 1854 as an insulating layer around nerve cells to improve electric signal propagation. Our study now shows that it also plays an important mechanical role: Using a combined mechanical characterization and histological characterization, we found that the white matter stiffness increases linearly with increasing myelin content, from 0.5kPa at a myelin content of 63-2.5kPa at 92%.

    View details for DOI 10.1016/j.actbio.2016.07.040

    View details for PubMedID 27475531

  • Tensile Instability in a Thick Elastic Body. Physical review letters Overvelde, J. T., Dykstra, D. M., de Rooij, R., Weaver, J., Bertoldi, K. 2016; 117 (9): 094301-?

    Abstract

    A range of instabilities can occur in soft bodies that undergo large deformation. While most of them arise under compressive forces, it has previously been shown analytically that a tensile instability can occur in an elastic block subjected to equitriaxial tension. Guided by this result, we conducted centimeter-scale experiments on thick elastomeric samples under generalized plane strain conditions and observed for the first time this elastic tensile instability. We found that equibiaxial stretching leads to the formation of a wavy pattern, as regions of the sample alternatively flatten and extend in the out-of-plane direction. Our work uncovers a new type of instability that can be triggered in elastic bodies, enlarging the design space for smart structures that harness instabilities to enhance their functionality.

    View details for DOI 10.1103/PhysRevLett.117.094301

    View details for PubMedID 27610857

  • Constitutive Modeling of Brain Tissue: Current Perspectives APPLIED MECHANICS REVIEWS de Rooij, R., Kuhl, E. 2016; 68 (1)

    View details for DOI 10.1115/1.4032436

    View details for Web of Science ID 000388740800001

  • Mechanical properties of gray and white matter brain tissue by indentation. Journal of the mechanical behavior of biomedical materials Budday, S., Nay, R., de Rooij, R., Steinmann, P., Wyrobek, T., Ovaert, T. C., Kuhl, E. 2015; 46: 318-330

    Abstract

    The mammalian brain is composed of an outer layer of gray matter, consisting of cell bodies, dendrites, and unmyelinated axons, and an inner core of white matter, consisting primarily of myelinated axons. Recent evidence suggests that microstructural differences between gray and white matter play an important role during neurodevelopment. While brain tissue as a whole is rheologically well characterized, the individual features of gray and white matter remain poorly understood. Here we quantify the mechanical properties of gray and white matter using a robust, reliable, and repeatable method, flat-punch indentation. To systematically characterize gray and white matter moduli for varying indenter diameters, loading rates, holding times, post-mortem times, and locations we performed a series of n=192 indentation tests. We found that indenting thick, intact coronal slices eliminates the common challenges associated with small specimens: it naturally minimizes boundary effects, dehydration, swelling, and structural degradation. When kept intact and hydrated, brain slices maintained their mechanical characteristics with standard deviations as low as 5% throughout the entire testing period of five days post mortem. White matter, with an average modulus of 1.895kPa±0.592kPa, was on average 39% stiffer than gray matter, p<0.01, with an average modulus of 1.389kPa±0.289kPa, and displayed larger regional variations. It was also more viscous than gray matter and responded less rapidly to mechanical loading. Understanding the rheological differences between gray and white matter may have direct implications on diagnosing and understanding the mechanical environment in neurodevelopment and neurological disorders.

    View details for DOI 10.1016/j.jmbbm.2015.02.024

    View details for PubMedID 25819199

  • Mechanical properties of gray and white matter brain tissue by indentation. Journal of the mechanical behavior of biomedical materials Budday, S., Nay, R., de Rooij, R., Steinmann, P., Wyrobek, T., Ovaert, T. C., Kuhl, E. 2015; 46: 318-330

    View details for DOI 10.1016/j.jmbbm.2015.02.024

    View details for PubMedID 25819199

  • A finite element interior-point implementation of tension field theory COMPUTERS & STRUCTURES de Rooij, R., Abdalla, M. M. 2015; 151: 30-41