Tissue-Level Mechanosensitivity: Predicting and Controlling the Orientation of 3D Vascular Networks

Shira Landau 1 Avraham Moriel 2 Ariel Livne 3 Ming Zheng 4 Eran Bouchbinder 2 Shulamit Levenberg 1
1Technion, Israel
2Weizmann Institute of Science, Israel
3Weizmann Institute of Science, Israel
4The University of Western Australia, Australia

Background: Understanding the mechanosensitivity of tissues is a fundamentally important problem having far-reaching implications for tissue engineering. Methods: Here we study vascular networks formed by a coculture of fibroblasts and endothelial cells embedded in three-dimensional biomaterials experiencing external, physiologically relevant forces. Results: We show that cyclic stretching of the biomaterial orients the newly formed network perpendicular to the stretching direction, independent of the geometric aspect ratio of the biomaterial’s sample. A two-dimensional theory explains this observation in terms of the network’s stored elastic energy if the cell-embedded biomaterial features a vanishing effective Poisson’s ratio, which we directly verify. We further show that under a static stretch, vascular networks orient parallel to the stretching direction due to force-induced anisotropy of the biomaterial polymer network. Finally, static stretching followed by cyclic stretching reveals a competition between the two mechanosensitive mechanisms. Conclusion: These results demonstrate tissue-level mechanosensitivity and constitute an important step toward developing enhanced tissue repair capabilities using well-oriented vascular networks.

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