Ligand Mobility Modulates Immunological Synapse Formation and T Cell Activation

T cell receptor (TCR) engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70) and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76). This molecular rearrangement results in formation of the immunological synapse (IS), a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC) formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC) dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses

Recent advances in electrospun polycaprolactone based scaffolds for wound healing and skin bioengineering applications

Electrospun poly(-caprolactone) (PCL) scaffolds incorporated with bioactive materials play a key role in tissue engineering applications due to their extra cellular matrix (ECM) mimicking property, biocompatibility and biodegradability. Electrospinning is one of the most successful techniques for the fabrication of nonwoven, three-dimensional, porous, and nano or submicron scale fiber-based matrices with tunable morphology. Investigations on the use of electrospun PCL and its blends/composites for skin reconstruction has gained much momentum recently. Feasibility of improving the cell attachment and antimicrobial properties of scaffolds by incorporating active agents such as growth factors, medications and nanomaterials have been frequently investigated. For rapid wound healing, electrospun wound dressings/skin substitutes should be able to accelerate wound healing and enhance cell proliferation. Gradual degradation of the scaffold along with tissue regeneration is also very important. Thus, carefully designed scaffolds that can improve the skin regeneration along with the potential to promote rapid wound healing has become a promising strategy in tissue regeneration therapies. This review outlines, a comprehensive overview of electrospun PCL based scaffolds in the context of skin bioengineering and wound healing. It sought to give an understanding about the advances in electrospun PCL scaffolds after the incorporation of active agents and the need to take these advances from bench side to clinical practice

Structure-Thermal Conductivity Tentative Correlation for Hybrid Aerogels Based on Nanofibrillated Cellulose-Mesoporous Silica Nanocomposite

Hybrid aerogels have been prepared by freeze-drying technique after mixing water dispersions of cellulose microfibers or cellulose nanofibers and silica (SiO2) of type SBA-15 (2D-hexagonal). The prepared composites were characterized by different analysis techniques such as SEM, hot-filament, DMA, etc. These composites are compared to those previously prepared using nanozeolites (NZs) as mineral charge. The morphology studied by SEM indicated that both systems have different structures, i.e., individual fibers for cellulose microfibers WP-based aerogels and films for nanofibrillated cellulose NFC-based ones.... These differences seem to be driven by the charge of the particles, their aspect ratio and concentrations. These hybrid materials exhibit tunable thermal conductivity and mechanical properties. The thermal conductivity values range between ~18 to 28 mW. m–1. K–1and confirm the superinsulation ability of these fibrous aerogels. Synergism on the thermal insulation properties and mechanical properties was shown by adjunction of mineral particles to both cellulose-based aerogels by reaching pore size lower than 100 nm. It significantly reduces the thermal conductivity of the hybrid aerogels as predicted by Knudsen et al. Furthermore, the addition of mineral fillers to aerogels based on cellulose microfibers induced a significant increase in stiffness