Synthetic hydrogels can be used as scaffolds that not only favor endothelial cells （ECs） proliferation but also manipulate the behaviors and functions of the ECs. In this review paper, the effect of chemical structu...Synthetic hydrogels can be used as scaffolds that not only favor endothelial cells （ECs） proliferation but also manipulate the behaviors and functions of the ECs. In this review paper, the effect of chemical structure, Young＇s modulus （E） and zeta potential （ζ） of synthetic hydrogel scaffolds on static cell behaviors, including cell morphology, proliferation, cytoskeleton structure and focal adhesion, and on dynamic cell behaviors, including migration velocity and morphology oscillation, as well as on EC function such as anti-platelet adhesion, are reported. It was found that negatively charged hydrogels, poly（2-acrylamido-2-methylpropanesulfonic sodium） （PNaAMPS） and poly（sodium p-styrene sulphonate） （PNaSS）, can directly promote cell proliferation, with no need of surface modifcation by any cell-adhesive proteins or peptides at the environment of serum-containing medium. In addition, the Young＇s modulus （E） and zeta potential （ζ） of hydrogel scaffolds are quantitatively tuned by copolymer hydrogels, poly（NaAMPS-co-DMAAm） and poly（NaSS-co-DMAAm）, in which the two kinds of negatively charged monomers NaAMPS and NaSS are copolymerized with neutral monomer, N,N-dimethylacrylamide （DMAAm）. It was found that the critical zeta potential of hydrogels manipulating EC morphology, proliferation, and motility is ζcritical= -20.83 mV and ζcritical = -14.0 mV for poly（NaAMPS-co-DMAAm） and poly（NaSS-co-DMAAm）, respectively. The above mentioned EC behaviors well correlate with the adsorption of fibronectin, a kind of cell-adhesive protein, on the hydrogel surfaces. Furthermore, adhered platelets on the EC monolayers cultured on the hydrogel scaffolds obviously decreases with an increase of the Young＇s modulus （E） of the hydrogels, especially when E 〉 60 kPa. Glycocalyx assay and gene expression of ECs demonstrate that the anti-platelet adhesion well correlates with the EC-specific glycocalyx. The above investigation suggests that understanding the relation展开更多
Asymmetric cell division is an important mechanism for creating diversity in a cellular population. Stem cells commonly perform asymmetric division to generate both a daughter stem cell for self-renewal and a more dif...Asymmetric cell division is an important mechanism for creating diversity in a cellular population. Stem cells commonly perform asymmetric division to generate both a daughter stem cell for self-renewal and a more differentiated daughter cell to populate the tissue. During asymmetric cell division, protein cell fate determinants asymmetrically localize to the opposite poles of a dividing cell to cause distinct cell fate. However, it remains unclear whether cell fate determination is robust to fluctuations and noise during this spatial allocation process. To answer this question, we engineered Caulobacter, a bacterial model for asymmetric division, to express synthetic scaffolds with modular protein interaction domains. These scaffolds perturbed the spatial distribution of the PleC-DivJ- DivK phospho-signaling network without changing their endogenous expression levels. Surprisingly, enforcing symmetrical distribution of these cell fate de terminants did not result in symmetric daughter fate or any morphological defects. Further computational analysis suggested that PleC and DivJ form a robust phospho-switch that can tolerate high amount of spatial variation. This insight may shed light on the presence of similar phospho-switches in stem cell asymmetric division regulation. Overall, our study demonstrates that synthetic protein scaffolds can provide a useful tool to probe biological systems for better understanding of their operating principles.展开更多
The capability of human pluripotent stem cells(h PSCs) to differentiate into a variety of cells in the human body holds great promise for regenerative medicine. Many substrates exist on which h PSCs can be self-renewe...The capability of human pluripotent stem cells(h PSCs) to differentiate into a variety of cells in the human body holds great promise for regenerative medicine. Many substrates exist on which h PSCs can be self-renewed, maintained and expanded to further the goal of clinical application of stem cells. In this review, we highlight numerous extracellular matrix proteins, peptide and polymer based substrates, scaffolds and hydrogels that have been pioneered. We discuss their benefits and shortcomings and offer future directions as well as emphasize commercially available synthetic peptidesas a type of substrate that can bring the benefits of regenerative medicine to clinical settings.展开更多
文摘Synthetic hydrogels can be used as scaffolds that not only favor endothelial cells （ECs） proliferation but also manipulate the behaviors and functions of the ECs. In this review paper, the effect of chemical structure, Young＇s modulus （E） and zeta potential （ζ） of synthetic hydrogel scaffolds on static cell behaviors, including cell morphology, proliferation, cytoskeleton structure and focal adhesion, and on dynamic cell behaviors, including migration velocity and morphology oscillation, as well as on EC function such as anti-platelet adhesion, are reported. It was found that negatively charged hydrogels, poly（2-acrylamido-2-methylpropanesulfonic sodium） （PNaAMPS） and poly（sodium p-styrene sulphonate） （PNaSS）, can directly promote cell proliferation, with no need of surface modifcation by any cell-adhesive proteins or peptides at the environment of serum-containing medium. In addition, the Young＇s modulus （E） and zeta potential （ζ） of hydrogel scaffolds are quantitatively tuned by copolymer hydrogels, poly（NaAMPS-co-DMAAm） and poly（NaSS-co-DMAAm）, in which the two kinds of negatively charged monomers NaAMPS and NaSS are copolymerized with neutral monomer, N,N-dimethylacrylamide （DMAAm）. It was found that the critical zeta potential of hydrogels manipulating EC morphology, proliferation, and motility is ζcritical= -20.83 mV and ζcritical = -14.0 mV for poly（NaAMPS-co-DMAAm） and poly（NaSS-co-DMAAm）, respectively. The above mentioned EC behaviors well correlate with the adsorption of fibronectin, a kind of cell-adhesive protein, on the hydrogel surfaces. Furthermore, adhered platelets on the EC monolayers cultured on the hydrogel scaffolds obviously decreases with an increase of the Young＇s modulus （E） of the hydrogels, especially when E 〉 60 kPa. Glycocalyx assay and gene expression of ECs demonstrate that the anti-platelet adhesion well correlates with the EC-specific glycocalyx. The above investigation suggests that understanding the relation
文摘Asymmetric cell division is an important mechanism for creating diversity in a cellular population. Stem cells commonly perform asymmetric division to generate both a daughter stem cell for self-renewal and a more differentiated daughter cell to populate the tissue. During asymmetric cell division, protein cell fate determinants asymmetrically localize to the opposite poles of a dividing cell to cause distinct cell fate. However, it remains unclear whether cell fate determination is robust to fluctuations and noise during this spatial allocation process. To answer this question, we engineered Caulobacter, a bacterial model for asymmetric division, to express synthetic scaffolds with modular protein interaction domains. These scaffolds perturbed the spatial distribution of the PleC-DivJ- DivK phospho-signaling network without changing their endogenous expression levels. Surprisingly, enforcing symmetrical distribution of these cell fate de terminants did not result in symmetric daughter fate or any morphological defects. Further computational analysis suggested that PleC and DivJ form a robust phospho-switch that can tolerate high amount of spatial variation. This insight may shed light on the presence of similar phospho-switches in stem cell asymmetric division regulation. Overall, our study demonstrates that synthetic protein scaffolds can provide a useful tool to probe biological systems for better understanding of their operating principles.
文摘The capability of human pluripotent stem cells(h PSCs) to differentiate into a variety of cells in the human body holds great promise for regenerative medicine. Many substrates exist on which h PSCs can be self-renewed, maintained and expanded to further the goal of clinical application of stem cells. In this review, we highlight numerous extracellular matrix proteins, peptide and polymer based substrates, scaffolds and hydrogels that have been pioneered. We discuss their benefits and shortcomings and offer future directions as well as emphasize commercially available synthetic peptidesas a type of substrate that can bring the benefits of regenerative medicine to clinical settings.
