Abstract
There is a rapidly growing body of literature on the effects of topography and critically, nanotopography on cell adhesion, apoptosis and differentiation. Understanding the effects of nanotopography on cell adhesion and morphology and the consequences of cell shape changes in the nucleus, and consequently, gene expression offers new approaches to the elucidation and potential control of stem cell differentiation. In the current study we have used molecular approaches in combination with immunohistology and transcript analysis to understand the role of nanotopography on mesenchymal stem cell morphology and phenotype. Results demonstrate large changes in cell adhesion, nucleus and lamin morphologies in response to the different nanotopographies. Furthermore, these changes relate to alterations in packing of chromosome territories within the interphase nucleus. This, in turn, leads to changes in transcription factor activity and functional (phenotypical) signalling including cell metabolism. Nanotopography provides a useful, non-invasive tool for studying cellular mechanotransduction, gene and protein expression patterns, through effects on cell morphology. The different nanotopographies examined, result in different morphological changes in the cyto- and nucleo-skeleton. We propose that both indirect (biochemical) and direct (mechanical) signalling are important in these early stages of regulating stem cell fate as a consequence of altered metabolic changes and altered phenotype. The current studies provide new insight on cell-surface interactions and enhance our understanding of the modulation of stem cell differentiation with significant potential application in regenerative medicine.
Highlights
There is a rapidly growing body of literature on the effects of topography and critically, nanotopography on cell adhesion, apoptosis and differentiation
It is notable that vinculin staining of adhesions indicates much larger adhesion in mesenchymal stem cells (MSCs) on NSQ50 compared to cells on planar or on SQ (Fig. 1A insets) with cells on SQ utilising a number of smaller adhesions
We present a non‐invasive, in vitro model system that can be used to study osteogenesis or/and self‐renewal of MSCs
Summary
There is a rapidly growing body of literature on the effects of topography and critically, nanotopography on cell adhesion, apoptosis and differentiation. Understanding the effects of nanotopography on cell adhesion and morphology and the consequences of cell shape changes in the nucleus, and gene expression offers new approaches to the elucidation and potential control of stem cell differentiation. Results demonstrate large changes in cell adhesion, nucleus and lamin morphologies in response to the different nanotopographies. These changes relate to alterations in packing of chromosome territories within the interphase nucleus. The different nanotopographies examined, result in different morphological changes in the cyto‐ and nucleo‐skeleton We propose that both indirect (biochemical) and direct (mechanical) signalling are important in these early stages of regulating stem cell fate as a consequence of altered metabolic changes and altered phenotype. Direct mechanotransduction arises as a result of conformational changes in the cell cytoskeleton, forming direct links between the ECM and the cell nucleus through the nucleoskeletal lamins (the nuclear intermediate filaments) and possibly to the chromosomes themselves via telomeric chromatin/lamin interactions [Wang et al, 1993; Ingber, 1997]
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