scholarly journals Molecular control of interfacial protein structure on graphene-based substrates steers cell fate

2020 ◽  
Author(s):  
Sachin Kumar ◽  
Sapun H. Parekh

AbstractThe use of graphene-based materials (GBMs) for tissue-engineering applications is growing exponentially due to the seemingly endless multi-functional and tunable physicochemical properties of graphene, which can be exploited to influence cellular behaviours. Despite many demonstrations wherein cell physiology can be modulated on GBMs, a clear mechanism connecting the different physicochemical properties of different GBMs to cell fate has remained elusive. In this work, we demonstrate how different GBMs can be used to cell fate in a multi-scale study – starting from serum protein (Fibronectin) adsorption to molecular scale morphology, structure and bioactivity, and finally ending with stem cell response. By changing the surface chemistry of graphene substrates with only heating, we show that molecular conformation and morphology of surface adsorbed fibronectin controls epitope presentation, integrin binding, and stem cell attachment. Moreover, this subtle change in protein structure is found to drive increased bone differentiation of cells, suggesting that physicochemical properties of graphene substrates exert cell control by influencing adsorbed protein structure.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Céline Labouesse ◽  
Bao Xiu Tan ◽  
Chibeza C. Agley ◽  
Moritz Hofer ◽  
Alexander K. Winkel ◽  
...  

AbstractStudies of mechanical signalling are typically performed by comparing cells cultured on soft and stiff hydrogel-based substrates. However, it is challenging to independently and robustly control both substrate stiffness and extracellular matrix tethering to substrates, making matrix tethering a potentially confounding variable in mechanical signalling investigations. Moreover, unstable matrix tethering can lead to poor cell attachment and weak engagement of cell adhesions. To address this, we developed StemBond hydrogels, a hydrogel in which matrix tethering is robust and can be varied independently of stiffness. We validate StemBond hydrogels by showing that they provide an optimal system for culturing mouse and human pluripotent stem cells. We further show how soft StemBond hydrogels modulate stem cell function, partly through stiffness-sensitive ERK signalling. Our findings underline how substrate mechanics impact mechanosensitive signalling pathways regulating self-renewal and differentiation, indicating that optimising the complete mechanical microenvironment will offer greater control over stem cell fate specification.


2020 ◽  
Author(s):  
Mahetab H. Amer ◽  
Marta Alvarez-Paino ◽  
Jane McLaren ◽  
Francesco Pappalardo ◽  
Sara Trujillo ◽  
...  

AbstractMesenchymal stem cells have been the focus of intense research in bone development and regeneration. We demonstrate the potential of microparticles as modulating moieties of osteogenic response by utilizing their architectural features. Topographically textured microparticles of varying microscale features were produced by exploiting phase-separation of a readily-soluble sacrificial component from polylactic acid. The influence of varying topographical features on primary human mesenchymal stem cell attachment, proliferation and markers of osteogenesis was investigated. In the absence of osteoinductive supplements, cells cultured on textured microparticles exhibited notably increased expression of osteogenic markers relative to conventional smooth microparticles. They also exhibited varying morphological, attachment and proliferation responses. Significantly altered gene expression and metabolic profiles were observed, with varying histological characteristics in vivo. This study highlights how tailoring topographical design offers cell-instructive 3D microenvironments which allow manipulation of stem cell fate by eliciting the desired downstream response without use of exogenous osteoinductive factors.


2014 ◽  
Vol 21 (19) ◽  
pp. 2190-2207 ◽  
Author(s):  
S. Schildge ◽  
C. Bohrer ◽  
S. Pfurr ◽  
K. Mammadzada ◽  
K. Schachtrup ◽  
...  

2019 ◽  
Vol 26 (34) ◽  
pp. 6321-6338 ◽  
Author(s):  
Shuaimeng Guan ◽  
Kun Zhang ◽  
Jingan Li

Stem cell transplantation is an advanced medical technology, which brings hope for the treatment of some difficult diseases in the clinic. Attributed to its self-renewal and differential ability, stem cell research has been pushed to the forefront of regenerative medicine and has become a hot topic in tissue engineering. The surrounding extracellular matrix has physical functions and important biological significance in regulating the life activities of cells, which may play crucial roles for in situ inducing specific differentiation of stem cells. In this review, we discuss the stem cells and their engineering application, and highlight the control of the fate of stem cells, we offer our perspectives on the various challenges and opportunities facing the use of the components of extracellular matrix for stem cell attachment, growth, proliferation, migration and differentiation.


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