Dynamic Tensile Loading Activates TGF and BMP Signaling in Mesenchymal Stem Cells on Aligned Nanofibrous Scaffolds

Mesenchymal stem cells (MSCs) are a promising cell source for tissue engineering applications, given their ease of isolation and multi-potential differentiation capacity [1]. External mechanical cues directly influence MSC lineage commitment [2]. However, it is not yet clear how these physical cues are transduced to the cell nucleus, an understanding of which may prove essential for orthopaedic tissue engineering. Transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP), members of the TGF beta superfamily, regulate cellular processes including growth and differentiation [3, 4]. TGF and/or BMP ligand binding initiate SMAD phosphorylation, translocation to the nucleus, and transcriptional activation of target genes [4]. Additionally, both ligands can influence the organization of chromatin and the Lamin A/C (LMAC) nucleoskeletal network [5]. For example, we have recently shown that TGF-β3 leads to corticalized LMAC, marked increases in heterochromatin (HTC), and increased nuclear stiffness [6]. Interestingly, dynamic tensile stretch of MSCs on aligned nanofibrous scaffolds, in the absence of these differentiation factors, resulted in many of these same nuclear transformations [6, 7]. The objective of this study was to identify how dynamic tensile stress is transduced in MSCs on aligned nanofibrous scaffolds, and further, to ascertain whether these mechanoregulatory changes are coordinated through TGFβ/BMP signaling pathways.