Reorganization of Cytoskeleton and Transient Activation of Ca²⁺ Channels in Mesenchymal Stem Cells Cultured on Silicon Nanowire Arrays

Abstract

Tissue engineering combines biological cells and synthetic materials containing chemical signaling molecules to form scaffolds for tissue regeneration. Mesenchymal stem cells (MSCs) provide an attractive source for tissue engineering due to their versatility of multipotent differentiation. Recently, it has been recognized that both chemical and mechanical stimulations are essential mediators of adhesion and differentiation of MSCs. While significant progress has been made on the understanding of chemical regulatory factors within the extracellular matrix, the effects of mechanical stimulation exerted by nanomaterials on MSCs and the underlying mechanisms are less well-known. The present study showed that the adhesion, proliferation, and differentiation of MSCs cultured on vertically aligned silicon nanowire (SiNW) arrays were significantly different from those on flat silicon wafer and control substrates. The interactions between MSCs and the SiNW arrays caused the stem cells to preferentially differentiate toward osteocytes and chondrocytes but not adipocytes in the absence of supplementary growth factors. Our study demonstrated that Ca(2+) ion channels were transiently activated in MSCs upon mechanical stimulation, which eventually led to activation of Ras/Raf/MEK/ERK signaling cascades to regulate adhesion, proliferation, and differentiation of MSCs. The stretch-mediated transient Ca(2+) ion channel activation and cytoskeleton reorganization during stem cell-nanowire interaction may be early events of lineage-specific potentiation of MSCs in determining the fates of mesenchymal stem cells cultured on microenvironments with specific mechanical properties.

Graphene/single-walled carbon nanotube hybrids promoting osteogenic differentiation of mesenchymal stem cells by activating p38 signaling pathway

“…22 Based on the gene expression data, it was further confirmed that G/SWCNT hybrids could promote osteogenic differentiation and not adipogenic lineage of rMSCs, as evidenced by the upregulation of the osteogenic lineage-associated markers and downregulation of the adipogenic differentiation marker.…”

“…7 In addition to carbon nanomaterials, other types of nanomaterials, such as gold, titanium, silicon, and hydroxyapatite, also exhibit the potential to enhance differentiation. 8,[21][22][23] The earlier studies contain crucial literature as a basis for further exploration of the possible uses of G/SWCNT hybrids for bone repair and regeneration using stem cells.…”

Vertical SiNWAs for biomedical and biotechnology applications

“…75 The interactions between MSCs and SiNWAs caused the stem cells to preferentially differentiate toward osteocytes and chondrocytes but not adipocytes in the absence of supplementary growth factors. 75 The interactions between MSCs and SiNWAs caused the stem cells to preferentially differentiate toward osteocytes and chondrocytes but not adipocytes in the absence of supplementary growth factors.…”

Micro‐ and Nanotechnologies for Intracellular Delivery

“…For example, mesenchymal stem cells cultured on silicon nanowires show significantly different behaviors of adhesion, proliferation, and differentiation, compared with flat silicon or control substrates. This interaction between mesenchymal stem cells and SiNWs can induce the stem cells to differentiate toward osteocytes and chondrocytes instead of adipocytes in the absence of supplementary growth factors . In addition, Persson et al reported fibroblasts cultured on nanowires exhibiting low motility, impaired cell division, and DNA damage .…”