Department of Biomedical Engineering, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
Department of Chemical Engineering, University of Minnesota - Duluth, Duluth, MN, USA.
J R Soc Interface. 2022 May;19(190):20210951. doi: 10.1098/rsif.2021.0951. Epub 2022 May 18.
Despite its importance in physiological processes and tissue engineering, the mechanism underlying cell contact guidance in an aligned fibrillar network has defied elucidation due to multiple interdependent signals that such a network presents to cells, namely, anisotropy of adhesion, porosity and mechanical behaviour. A microstructural-mechanical model of fibril networks was used to assess the relative magnitudes of these competing signals in networks of varied alignment strength based on idealized cylindrical pseudopods projected into the aligned and orthogonal directions and computing the anisotropy of metrics chosen for adhesion, porosity and mechanical behaviour: cylinder-fibre contact area for adhesion, persistence length of pores for porosity and total force to displace fibres from the cylindrical volume as well as network stiffness experienced upon cylinder retraction for mechanical behaviour. The signals related to mechanical anisotropy are substantially higher than adhesion and porosity anisotropy, especially at stronger network alignments, although their signal to noise (S/N) values are substantially lower. The former finding is consistent with a recent report that fibroblasts can sense fibril alignment via anisotropy of network mechanical resistance, and the model reveals this can be due to either mechanical resistance to pseudopod protrusion or retraction given their signal and S/N values are similar.
尽管细胞接触导向在生理过程和组织工程中具有重要意义，但由于这种纤维网络向细胞呈现出多个相互依存的信号，例如粘附各向异性、孔隙率和机械性能，因此其背后的机制仍然难以阐明。本文使用纤维网络的微观力学模型，根据理想的圆柱形伪足在纤维网络中的取向强度，评估了这些竞争信号的相对大小，通过将圆柱形伪足投影到取向和垂直方向，计算出用于粘附、孔隙率和机械性能的度量的各向异性：粘附的圆柱纤维接触面积、孔隙率的持久长度和从圆柱体积中移出纤维的总力，以及圆柱缩回时网络刚度。与机械各向异性相关的信号远高于粘附和孔隙率各向异性，尤其是在纤维网络取向更强的情况下，尽管它们的信噪比（S/N）值要低得多。这一发现与最近的一项研究报告一致，即成纤维细胞可以通过网络机械阻力的各向异性来感知纤维的取向，而该模型揭示了这可能是由于伪足的伸出或缩回的机械阻力，因为它们的信号和 S/N 值相似。
