Mechanical Control of Stem Cell Differentiation

Dado, Dekel; Sagi, Maayan; Levenberg, Shulamit; Zemel, A.

doi:10.2217/rme.11.99

Cited by 63 publications

(44 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although actin expression was comparable between the stiff and soft substrate, the expression of vimentin and a-tubulin was higher on the stiff substrate than on the soft substrate. These brief results supported the existing observations that substrate stiffness regulates rBMSC proliferation, morphology, differentiation, and cytoskeletal reorganization [5,13,24,25,28,35,36].…”

Section: Rbmscs On 3d and Planar Substratessupporting

confidence: 90%

Differential regulation of stiffness, topography, and dimension of substrates in rat mesenchymal stem cells

et al. 2013

View full text Add to dashboard Cite

a b s t r a c tThe physiological microenvironment of the stem cell niche, including the three factors of stiffness, topography, and dimension, is crucial to stem cell proliferation and differentiation. Although a growing body of evidence is present to elucidate the importance of these factors individually, the interaction of the biophysical parameters of the factors remains insufficiently characterized, particularly for stem cells. To address this issue fully, we applied a micro-fabricated polyacrylamide hydrogel substrate with two elasticities, two topographies, and three dimensions to systematically test proliferation, morphology and spreading, differentiation, and cytoskeletal re-organization of rat bone marrow mesenchymal stem cells (rBMSCs) on twelve cases. An isolated but not combinatory impact of the factors was found regarding the specific functions. Substrate stiffness or dimension is predominant in regulating cell proliferation by fostering cell growth on stiff, unevenly dimensioned substrate. Topography is a key factor for manipulating cell morphology and spreading via the formation of a large spherical shape in a pillar substrate but not in a grooved substrate. Although stiffness leads to osteogenic or neuronal differentiation of rBMSCs on a stiff or soft substrate, respectively, topography or dimension also plays a lesser role in directing cell differentiation. Neither an isolated effect nor a combinatory effect was found for actin or tubulin expression, whereas a seemingly combinatory effect of topography and dimension was found in manipulating vimentin expression. These results further the understandings of stem cell proliferation, morphology, and differentiation in a physiologically mimicking microenvironment.

show abstract

Section: Rbmscs On 3d and Planar Substratessupporting

confidence: 90%

Differential regulation of stiffness, topography, and dimension of substrates in rat mesenchymal stem cells

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The answer appears to be yes. For example, it is becoming apparent that cell growth and cell behavior depend on the mechanical and geometric properties of the cell environment (in addition to the biochemical environment) [54][55][56]. Thus, one goal in tissue engineering is to mimic the structural and mechanical properties of the extracellular matrix, and electrospun nanofibers match the dimensions of fibers in the extracellular matrix well.…”

Section: Discussionmentioning

confidence: 99%

Determining the mechanical properties of electrospun poly-ε-caprolactone (PCL) nanofibers using AFM and a novel fiber anchoring technique

Baker

Banerjee

Bonin

et al. 2016

Materials Science and Engineering: C

184

View full text Add to dashboard Cite

Due to its low cost, biocompatibility and slow bioresorption, poly-ε-caprolactone (PCL) continues to be a suitable material for select biomedical engineering applications. We used a combined atomic force microscopy (AFM)/optical microscopy technique to determine key mechanical properties of individual electrospun PCL nanofibers with diameters between 440-1040nm. Compared to protein nanofibers, PCL nanofibers showed much lower adhesion, as they slipped on the substrate when mechanically manipulated. We, therefore, first developed a novel technique to anchor individual PCL nanofibers to micrometer-sized ridges on a substrate, and then mechanically tested anchored nanofibers. When held at constant strain, tensile stress relaxed with fast and slow relaxation times of 1.0±0.3s and 8.8±3.1s, respectively. The total tensile modulus was 62±26MPa, the elastic (non-relaxing) component of the tensile modulus was 53±36MPa. Individual PCL fibers could be stretched elastically (without permanent deformation) to strains of 19-23%. PCL nanofibers are rather extensible; they could be stretched to a strain of at least 98%, and a tensile strength of at least 12MPa, before they slipped off the AFM tip. PCL nanofibers that had aged for over a month at ambient conditions became stiffer and less elastic. Our technique provides accurate nanofiber mechanical data, which are needed to guide construction of scaffolds for cells and other biomedical devices.

show abstract

“…[39][40][41] Cell-matrix molecular interactions have been revealed by numerous in vitro and in vivo experimental studies, but the relationship between specific cell types and the geometry of the surface to which they attach remains mostly to be analyzed. Nanotechnologies are useful for these studies because of the unique opportunity to utilize and modify diverse biocompatible materials and build substrates which differ only by topology.…”

Section: Discussionmentioning

confidence: 99%

A nanoporous surface is essential for glomerular podocyte differentiation in three-dimensional culture

Zennaro¹,

Rastaldi²,

Bakeine³

et al. 2016

IJN

View full text Add to dashboard Cite

Although it is well recognized that cell–matrix interactions are based on both molecular and geometrical characteristics, the relationship between specific cell types and the three-dimensional morphology of the surface to which they are attached is poorly understood. This is particularly true for glomerular podocytes – the gatekeepers of glomerular filtration – which completely enwrap the glomerular basement membrane with their primary and secondary ramifications. Nanotechnologies produce biocompatible materials which offer the possibility to build substrates which differ only by topology in order to mimic the spatial organization of diverse basement membranes. With this in mind, we produced and utilized rough and porous surfaces obtained from silicon to analyze the behavior of two diverse ramified cells: glomerular podocytes and a neuronal cell line used as a control. Proper differentiation and development of ramifications of both cell types was largely influenced by topographical characteristics. Confirming previous data, the neuronal cell line acquired features of maturation on rough nanosurfaces. In contrast, podocytes developed and matured preferentially on nanoporous surfaces provided with grooves, as shown by the organization of the actin cytoskeleton stress fibers and the proper development of vinculin-positive focal adhesions. On the basis of these findings, we suggest that in vitro studies regarding podocyte attachment to the glomerular basement membrane should take into account the geometrical properties of the surface on which the tests are conducted because physiological cellular activity depends on the three-dimensional microenvironment.

show abstract

Mechanical Control of Stem Cell Differentiation

Cited by 63 publications

References 143 publications

Differential regulation of stiffness, topography, and dimension of substrates in rat mesenchymal stem cells

Differential regulation of stiffness, topography, and dimension of substrates in rat mesenchymal stem cells

Determining the mechanical properties of electrospun poly-ε-caprolactone (PCL) nanofibers using AFM and a novel fiber anchoring technique

A nanoporous surface is essential for glomerular podocyte differentiation in three-dimensional culture

Contact Info

Product

Resources

About