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Modulus of Fibrous Collagen at the Length Scale of a Cell

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Abstract

The extracellular matrix provides macroscale structural support to tissues as well as microscale mechanical cues, like stiffness, to the resident cells. As those cues modulate gene expression, proliferation, differentiation, and motility, quantifying the stiffness that cells sense is crucial to understanding cell behavior. Whereas the macroscopic modulus of a collagen network can be measured in uniform extension or shear, quantifying the local stiffness sensed by a cell remains a challenge due to the inhomogeneous and nonlinear nature of the fiber network at the scale of the cell. To address this challenge, we designed an experimental method to measure the modulus of a network of collagen fibers at this scale. We used spherical particles of an active hydrogel (poly N-isopropylacrylamide) that contract when heated, thereby applying local forces to the collagen matrix and mimicking the contractile forces of a cell. After measuring the particles’ bulk modulus and contraction in networks of collagen fibers, we applied a nonlinear model for fibrous materials to compute the modulus of the local region surrounding each particle. We found the modulus at this length scale to be highly heterogeneous, with modulus varying by a factor of 3. In addition, at different values of applied strain, we observed both strain stiffening and strain softening, indicating nonlinearity of the collagen network. Thus, this experimental method quantifies local mechanical properties in a fibrous network at the scale of a cell, while also accounting for inherent nonlinearity.

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Acknowledgments

We thank the Materials Science Center at the University of Wisconsin–Madison, which provided access to the spinning disk confocal microscope. This work was supported in part by NIH NCI P30CA014520–UW Comprehensive Cancer Center Support Grant and National Science Foundation grant number CMMI-1749400.

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Authors and Affiliations

  1. Department of Engineering Physics, University of Wisconsin–Madison, Madison, WI, USA

    M. Proestaki, A. Ogren, B. Burkel & J. Notbohm

  2. University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    J. Notbohm

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  1. M. Proestaki
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Proestaki, M., Ogren, A., Burkel, B. et al. Modulus of Fibrous Collagen at the Length Scale of a Cell. Exp Mech 59, 1323–1334 (2019). https://doi.org/10.1007/s11340-018-00453-4

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