Stretching of porous poly (l-lactide-co-ε-caprolactone) membranes regulates the differentiation of mesenchymal stem cells

Background: Among a variety of biomaterials supporting cell growth for therapeutic applications, poly (l-lactide-co-ε-caprolactone) (PLCL) has been considered as one of the most attractive scaffolds for tissue engineering owing to its superior mechanical strength, biocompatibility, and processibility. Although extensive studies have been conducted on the relationship between the microstructure of polymeric materials and their mechanical properties, the use of the fine-tuned morphology and mechanical strength of PLCL membranes in stem cell differentiation has not yet been studied.Methods: PLCL membranes were crystallized in a combination of diverse solvent–nonsolvent mixtures, including methanol (MeOH), isopropanol (IPA), chloroform (CF), and distilled water (DW), with different solvent polarities. A PLCL membrane with high mechanical strength induced by limited pore formation was placed in a custom bioreactor mimicking the reproducible physiological microenvironment of the vascular system to promote the differentiation of mesenchymal stem cells (MSCs) into smooth muscle cells (SMCs).Results: We developed a simple, cost-effective method for fabricating porosity-controlled PLCL membranes based on the crystallization of copolymer chains in a combination of solvents and non-solvents. We confirmed that an increase in the ratio of the non-solvent increased the chain aggregation of PLCL by slow evaporation, leading to improved mechanical properties of the PLCL membrane. Furthermore, we demonstrated that the cyclic stretching of PLCL membranes induced MSC differentiation into SMCs within 10 days of culture.Conclusion: The combination of solvent and non-solvent casting for PLCL solidification can be used to fabricate mechanically durable polymer membranes for use as mechanosensitive scaffolds for stem cell differentiation

External push and internal pull forces recruit curvature-sensing N-BAR domain proteins to the plasma membrane

Many of the more than 20 mammalian proteins with N-BAR domains1-2 control cell architecture3 and endocytosis4-5 by associating with curved sections of the plasma membrane (PM)6. It is not well understood whether N-BAR proteins are recruited directly by processes that mechanically curve the PM or indirectly by PM-associated adaptor proteins that recruit proteins with N-BAR domains that then induce membrane curvature. Here, we show that externally-induced inward deformation of the PM by cone-shaped nanostructures (Nanocones) and internally-induced inward deformation by contracting actin cables both trigger recruitment of isolated N-BAR domains to the curved PM. Markedly, live-cell imaging in adherent cells showed selective recruitment of full length N-BAR proteins and isolated N-BAR domains to PM sub-regions above Nanocone stripes. Electron microscopy confirmed that N-BAR domains are recruited to local membrane sites curved by Nanocones. We further showed that N-BAR domains are periodically recruited to curved PM sites during local lamellipodia retraction in the front of migrating cells. Recruitment required Myosin II-generated force applied to PM connected actin cables. Together, our study shows that N-BAR domains can be directly recruited to the PM by external push or internal pull forces that locally curve the PM

Ketohexokinase-mediated fructose metabolism is lost in hepatocellular carcinoma and can be leveraged for metabolic imaging

The ability to break down fructose is dependent on ketohexokinase (KHK) that phosphorylates fructose to fructose-1-phosphate (F1P). We show that KHK expression is tightly controlled and limited to a small number of organs and is down-regulated in liver and intestinal cancer cells. Loss of fructose metabolism is also apparent in hepatocellular adenoma and carcinoma (HCC) patient samples. KHK overexpression in liver cancer cells results in decreased fructose flux through glycolysis. We then developed a strategy to detect this metabolic switch in vivo using hyperpolarized magnetic resonance spectroscopy. Uniformly deuterating [2-13C]-fructose and dissolving in D2O increased its spin-lattice relaxation time (T1) fivefold, enabling detection of F1P and its loss in models of HCC. In summary, we posit that in the liver, fructolysis to F1P is lost in the development of cancer and can be used as a biomarker of tissue function in the clinic using metabolic imaging

Fast and Scalable Printing of Large Area Monolayer Nanoparticles for Nanotexturing Applications

Recently, there have been several studies demonstrating that highly ordered nanoscale texturing can dramatically increase performance of applications such as light absorption in thin-film solar cells. However, those methods used to make the nanostructures are not compatible with large-scale fabrication. Here we demonstrate that a technique currently used in roll-to-roll processing to deposit uniform thin films from solution, a wire-wound rod coating method, can be adapted to deposit close-packed monolayers or multilayers of silica nanoparticles on a variety of rigid and flexible substrates. Amorphous silicon thin films deposited on these nanoparticle monolayers exhibit 42% higher absorption over the integrated AM 1.5 spectrum than the planar controls. This simple assembly technique can be used to improve solar cells, fuel cells, light emitting diodes and other devices where ordered nanoscale texturing is critical for optimal performance.

Stepwise Nanopore Evolution in One-Dimensional Nanostructures

We report that established simple lithium (Li) ion battery cycles can be used to produce nanopores inside various useful one-dimensional (1D) nanostructures such as zinc oxide, silicon, and silver nanowires. Moreover, porosities of these 1D nanomaterials can be controlled in a stepwise manner by the number of Li-battery cycles. Subsequent pore characterization at the end of each cycle allows us to obtain detailed snapshots of the distinct pore evolution properties in each material due to their different atomic diffusion rates and types of chemical bonds. Also, this stepwise characterization led us to the first observation of pore size increases during cycling, which can be interpreted as a similar phenomenon to Ostwald ripening in analogous nanoparticle cases. Finally, we take advantage of the unique combination of nanoporosity and 1D materials and demonstrate nanoporous silicon nanowires (poSiNWs) as excellent supercapacitor (SC) electrodes in high power operations compared to existing devices with activated carbon.

Micro-Slab Coil Design for Hyperpolarized Metabolic Flux Analysis in Multiple Samples

Abnormal metabolism is a hallmark of cancer cells. Accumulating evidence suggests that metabolic changes are likely to occur before other cellular responses in cancer cells upon drug treatment. Therefore, the metabolic activity or flux in cancer cells could be a potent biomarker for cancer detection and treatment monitoring. Magnetic resonance (MR)-based sensing technologies have been developed with hyperpolarized molecules for real-time flux analysis, but they still suffer from low sensitivity and throughput. To address this limitation, we have developed an innovative miniaturized MR coil, termed micro-slab MR coil, for simultaneous analysis of metabolic flux in multiple samples. Combining this approach with hyperpolarized probes, we were able to quantify the pyruvate-to-lactate flux in two different leukemic cell lines in a non-destructive manner, simultaneously. Further, we were able to rapidly assess flux changes with drug treatment in a single hyperpolarization experiment. This new multi-sample system has the potential to transform our ability to assess metabolic dynamics at scale

Highly conductive paper for energy-storage devices

Paper, invented more than 2,000 years ago and widely used today in our everyday lives, is explored in this study as a platform for energy-storage devices by integration with 1D nanomaterials. Here, we show that commercially available paper can be made highly conductive with a sheet resistance as low as 1 ohm per square (Ω/sq) by using simple solution processes to achieve conformal coating of single-walled carbon nanotube (CNT) and silver nanowire films. Compared with plastics, paper substrates can dramatically improve film adhesion, greatly simplify the coating process, and significantly lower the cost. Supercapacitors based on CNT-conductive paper show excellent performance. When only CNT mass is considered, a specific capacitance of 200 F/g, a specific energy of 30–47 Watt-hour/kilogram (Wh/kg), a specific power of 200,000 W/kg, and a stable cycling life over 40,000 cycles are achieved. These values are much better than those of devices on other flat substrates, such as plastics. Even in a case in which the weight of all of the dead components is considered, a specific energy of 7.5 Wh/kg is achieved. In addition, this conductive paper can be used as an excellent lightweight current collector in lithium-ion batteries to replace the existing metallic counterparts. This work suggests that our conductive paper can be a highly scalable and low-cost solution for high-performance energy storage devices

DataSheet1_Stretching of porous poly (l-lactide-co-ε-caprolactone) membranes regulates the differentiation of mesenchymal stem cells.docx

Background: Among a variety of biomaterials supporting cell growth for therapeutic applications, poly (l-lactide-co-ε-caprolactone) (PLCL) has been considered as one of the most attractive scaffolds for tissue engineering owing to its superior mechanical strength, biocompatibility, and processibility. Although extensive studies have been conducted on the relationship between the microstructure of polymeric materials and their mechanical properties, the use of the fine-tuned morphology and mechanical strength of PLCL membranes in stem cell differentiation has not yet been studied.Methods: PLCL membranes were crystallized in a combination of diverse solvent–nonsolvent mixtures, including methanol (MeOH), isopropanol (IPA), chloroform (CF), and distilled water (DW), with different solvent polarities. A PLCL membrane with high mechanical strength induced by limited pore formation was placed in a custom bioreactor mimicking the reproducible physiological microenvironment of the vascular system to promote the differentiation of mesenchymal stem cells (MSCs) into smooth muscle cells (SMCs).Results: We developed a simple, cost-effective method for fabricating porosity-controlled PLCL membranes based on the crystallization of copolymer chains in a combination of solvents and non-solvents. We confirmed that an increase in the ratio of the non-solvent increased the chain aggregation of PLCL by slow evaporation, leading to improved mechanical properties of the PLCL membrane. Furthermore, we demonstrated that the cyclic stretching of PLCL membranes induced MSC differentiation into SMCs within 10 days of culture.Conclusion: The combination of solvent and non-solvent casting for PLCL solidification can be used to fabricate mechanically durable polymer membranes for use as mechanosensitive scaffolds for stem cell differentiation.</p

Video1_Stretching of porous poly (l-lactide-co-ε-caprolactone) membranes regulates the differentiation of mesenchymal stem cells.MP4

Background: Among a variety of biomaterials supporting cell growth for therapeutic applications, poly (l-lactide-co-ε-caprolactone) (PLCL) has been considered as one of the most attractive scaffolds for tissue engineering owing to its superior mechanical strength, biocompatibility, and processibility. Although extensive studies have been conducted on the relationship between the microstructure of polymeric materials and their mechanical properties, the use of the fine-tuned morphology and mechanical strength of PLCL membranes in stem cell differentiation has not yet been studied.Methods: PLCL membranes were crystallized in a combination of diverse solvent–nonsolvent mixtures, including methanol (MeOH), isopropanol (IPA), chloroform (CF), and distilled water (DW), with different solvent polarities. A PLCL membrane with high mechanical strength induced by limited pore formation was placed in a custom bioreactor mimicking the reproducible physiological microenvironment of the vascular system to promote the differentiation of mesenchymal stem cells (MSCs) into smooth muscle cells (SMCs).Results: We developed a simple, cost-effective method for fabricating porosity-controlled PLCL membranes based on the crystallization of copolymer chains in a combination of solvents and non-solvents. We confirmed that an increase in the ratio of the non-solvent increased the chain aggregation of PLCL by slow evaporation, leading to improved mechanical properties of the PLCL membrane. Furthermore, we demonstrated that the cyclic stretching of PLCL membranes induced MSC differentiation into SMCs within 10 days of culture.Conclusion: The combination of solvent and non-solvent casting for PLCL solidification can be used to fabricate mechanically durable polymer membranes for use as mechanosensitive scaffolds for stem cell differentiation.</p