Accomplishing on‐demand molecular separation with a high selectivity and good permeability is very desirable for pollutant removal and chemical and pharmaceutical processing. The major challenge for ...sub‐10 nm filtration of particles and molecules is the fabrication of high‐performance membranes with tunable pore size and designed functionality. Here, a versatile top‐down approach is demonstrated to produce such a membrane using isoporous block copolymer membranes with well‐defined pore sizes combined with growth of metal oxide using sequential infiltration synthesis and atomic layer deposition (SIS and ALD). The pore size of the membranes is tuned by controlled metal oxide growth within and onto the polymer channels, enabling up to twofold pore diameter reduction. Following the growth, the distinct functionalities are readily incorporated along the membrane nanochannels with either hydrophobic, cationic, or anionic groups via straightforward and scalable gas/liquid–solid interface reactions. The hydrophilicity/hydrophobicity of the membrane nanochannel is significantly changed by the introduction of hydrophilic metal oxide and hydrophobic fluorinated groups. The functionalized membranes exhibit a superior selectivity and permeability in separating 1–2 nm organic molecules and fractionating similar‐sized proteins based on size, charge, and hydrophobicity. This demonstrates the great potential of organic–inorganic–organic isoporous membranes for high‐performance molecular separation in numerous applications.
Novel hybrid organic–inorganic–organic isoporous membranes are fabricated via sequential infiltration synthesis and atomic layer deposition within block copolymer membranes followed by addition of functional organic molecules. The membrane pore sizes are controlled by metal oxide growth in a predictive manner. The hybrid membranes exhibit superior selectivity and permeability in separating 1–2 nm organic molecules and similar‐sized proteins.
Understanding the role of stability strengths and weaknesses in proteins is a key objective for rationalizing their dynamical and functional properties such as conformational changes, catalytic ...activity, and protein-protein and protein-ligand interactions. We present BRANEart, a new, fast and accurate method to evaluate the per-residue contributions to the overall stability of membrane proteins. It is based on an extended set of recently introduced statistical potentials derived from membrane protein structures, which better describe the stability properties of this class of proteins than standard potentials derived from globular proteins. We defined a per-residue membrane propensity index from combinations of these potentials, which can be used to identify residues which strongly contribute to the stability of the transmembrane region or which would, on the contrary, be more stable in extramembrane regions, or
vice versa
. Large-scale application to membrane and globular proteins sets and application to tests cases show excellent agreement with experimental data. BRANEart thus appears as a useful instrument to analyze in detail the overall stability properties of a target membrane protein, to position it relative to the lipid bilayer, and to rationally modify its biophysical characteristics and function. BRANEart can be freely accessed from
http://babylone.3bio.ulb.ac.be/BRANEart
.
Overexpressed extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDAC) limits drug penetration into the tumor and is associated with poor prognosis. Here, we demonstrate that a ...pretreatment based on a proteolytic-enzyme nanoparticle system disassembles the dense PDAC collagen stroma and increases drug penetration into the pancreatic tumor. More specifically, the collagozome, a 100 nm liposome encapsulating collagenase, was rationally designed to protect the collagenase from premature deactivation and prolonged its release rate at the target site. Collagen is the main component of the PDAC stroma, reaching 12.8 ± 2.3% vol in diseased mice pancreases, compared to 1.4 ± 0.4% in healthy mice. Upon intravenous injection of the collagozome, ∼1% of the injected dose reached the pancreas over 8 h, reducing the level of fibrotic tissue to 5.6 ± 0.8%. The collagozome pretreatment allowed increased drug penetration into the pancreas and improved PDAC treatment. PDAC tumors, pretreated with the collagozome followed by paclitaxel micelles, were 87% smaller than tumors pretreated with empty liposomes followed by paclitaxel micelles. Interestingly, degrading the ECM did not increase the number of circulating tumor cells or metastasis. This strategy holds promise for degrading the extracellular stroma in other diseases as well, such as liver fibrosis, enhancing tissue permeability before drug administration.
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Tin oxide (SnO2) nanostructures are attractive for sensing, catalysis, and optoelectronic applications. Here we investigate the fabrication of SnOx nanostructures through sequential ...infiltration synthesis (SIS) in block copolymer (BCP) film templates. While the growth of metal and metal oxides within polymers and BCP films via SIS has been demonstrated until now using small precursors such as trimethyl aluminum and diethyl zinc, we hypothesize that SIS can be performed using larger precursors and demonstrate SnOx SIS with tetrakis(dimethylamino)tin (TDMASn) and hydrogen peroxide. Tuning the SIS reaction and BCP chemistry resulted in highly ordered, polystyrene-block-poly(2-vinyl pyridine) (P2VP)-templated porous SnOx - AlOx and SnOx nanostructures. Detailed investigation using in-situ microbalance, high resolution electron microscopy, elemental analysis and infra-red spectroscopy shows that SnOx can directly grow within P2VP homopolymer and BCP films. Simultaneously with the growth, SnOx SIS process also contributes to the polymer etch. Performing SnOx SIS with pretreatment of a single AlOx SIS cycle increases the SnOx growth and protects the BCP template from etching. This is the first report of SnOx SIS opening a pathway for additional tetrakis-based organometallic precursors to be utilized in growth processes within polymers.
Surgical blades are common medical tools. However, blades cannot distinguish between healthy and diseased tissue, thereby creating unnecessary damage, lengthening recovery, and increasing pain. We ...propose that surgical procedures can rely on natural tissue remodeling tools-enzymes, which are the same tools our body uses to repair itself. Through a combination of nanotechnology and a controllably activated proteolytic enzyme, we performed a targeted surgical task in the oral cavity. More specifically, we engineered nanoparticles that contain collagenase in a deactivated form. Once placed at the surgical site, collagenase was released at a therapeutic concentration and activated by calcium, its biological cofactor that is naturally present in the tissue. Enhanced periodontal remodeling was recorded due to enzymatic cleavage of the supracrestal collagen fibers that connect the teeth to the underlying bone. When positioned in their new orientation, natural tissue repair mechanisms supported soft and hard tissue recovery and reduced tooth relapse. Through the combination of nanotechnology and proteolytic enzymes, localized surgical procedures can now be less invasive.
Molecular Communications is a research area which combines the expertise of two main fields of science: biology and engineering. This multidisciplinarity, in addition to being a fruitful strength, ...makes knowledge exchange between researchers difficult. This issue has led to the definition of a new markup language, named Molecular Communication Markup Language (MolComML). It contributes to the harmonization of cross-disciplinary research activities. By leveraging the typical flexibility of markup languages, it specifies the essential components of generic molecular communication scenarios, by combining both numerical analysis and experimental synthesis. In this paper we illustrate the architecture of MolComML and focus on its peculiarities that allow describing molecular communications systems. In addition, we evaluate the performance of some molecular communication systems by using different simulation packages, configured by using the MolComML, in order to demonstrate both its portability and the possibility of combining different platforms for creating complex simulation tools.
Drug delivery is one of the most important applications of molecular communication. Drug transmitters have limited resources in terms of energy and reservoir and these limitations should be taken ...into consideration when designing a drug delivery system. Drug molecules may also be expensive and releasing a large amount of them can have harmful effects on the healthy parts of the body. In this paper, we consider a multiple transmitter local drug delivery system in which the nearest transmitters to a randomly located tumor are activated to release drug molecules and guarantee the Least Effective Concentration (LEC) in every part of the tumor. We propose two different scenarios: a single transmitter drug delivery system for which the optimal rate of the transmitting nanomachine and the optimal density of deployed nanomachines are derived through formulations and simulations. Poisson distributed as well as regular square and hexagon grid deployments are investigated. We then extend it to a multiple transmitter drug delivery system for which the optimal allocated rate to each releasing transmitter is derived in order to minimize the total rate of release and maintain LEC in every part of the tumor. It is shown that activating multiple transmitters leads to a reduction in the total optimal release rate of drug molecules as well as improving the time duration between consecutive administrations.
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