Van Hest Research Articles

Compartmentalized Biomolecular Condensates via Controlled Nucleation.

This commentary underscores the importance and implications of the study "Biomolecular condensates with complex architectures via controlled nucleation," led by Jan C. M. van Hest and Tuomas P. J. Knowles, published in Nature Chemical Engineering. The research team developed a novel system to investigate the structure of biological condensates using quaternized amylose, carboxymethylated amylose, and single-stranded DNA. They successfully created multiphase droplets with distinct dense phases and demonstrated that droplet architecture can be controlled through temperature and salt concentration adjustments. This study offers valuable insights into the formation and function of membraneless organelles in cells and suggests promising applications for designing biomimetic materials and therapeutic strategies.

ChemSystemsChem – On the Up and Up

<i>ChemSystemsChem</i> – On the Up and Up

Machine learning with knowledge constraints for process optimization of open-air perovskite solar cell manufacturing

Machine learning with knowledge constraints for process optimization of open-air perovskite solar cell manufacturing

Cell Junction Mechanics beyond the Bounds of Adhesion and Tension.

Cell-cell junctions, in particular adherens junctions, are major determinants of tissue mechanics during morphogenesis and homeostasis. In attempts to link junctional mechanics to tissue mechanics, many have utilized explicitly or implicitly equilibrium approaches based on adhesion energy, surface energy, and contractility to determine the mechanical equilibrium at junctions. However, it is increasingly clear that they have significant limitations, such as that it remains challenging to link the dynamics of the molecular components to the resulting physical properties of the junction, to its remodeling ability, and to its adhesion strength. In this perspective, we discuss recent attempts to consider the aspect of energy dissipation at junctions to draw contact points with soft matter physics where energy loss plays a critical role in adhesion theories. We set the grounds for a theoretical framework of the junction mechanics that bridges the dynamics at the molecular scale to the mechanics at the tissue scale.

Assessing the Regulatory Requirements of Lead-Based Perovskite Photovoltaics

Nicole Moody, Samuel Sesena, Dane W. deQuilettes, Benjia Dak Dou, Richard Swartwout, Anna Johnson, Udochukwu Eze, Roberto Brenes, Matthew Johnston, Vladimir Bulovic, and Moungi G. Bawendi are members of Tata-MIT GridEdge Solar, an interdisciplinary research program at the Massachusetts Institute of Technology working toward scalable design and manufacturing of lightweight, flexible solar cells. Joseph T. Buchman and Christy L. Haynes are part of the Center for Sustainable Nanotechnology, a multi-institutional partnership aimed at understanding the fundamental chemical and physical processes that govern the transformations and interactions of nanoparticles in the environment.

Dissipative Self-Assembly of Dynamic Multicompartmentalized Microsystems with Light-Responsive Behaviors

Summary Living cells are compartmentalized systems operating far from thermodynamic equilibrium and consume energy from the environment to carry out their functions. The construction of biomimetic synthetic compartments has both scientific and technological value. Despite many advances, the assembly of synthetic compartments that present nonequilibrium behaviors based on dissipative (or transient) self-assembly remains a grand challenge. Here, we describe the design and synthesis of multicompartmental systems with an active microstructure and complex behaviors. By including an artificial pathway for energy dissipation, we demonstrate the autonomous generation of active polymeric systems using a strategy based on polymerization-induced self-assembly (PISA), driven by chemical fuel. Remarkably, these self-organized synthetic systems exhibit a dynamic change in their multicompartmental structures when exposed to light. This work introduces a strategy toward the design and construction of synthetic compartments with a dynamic structure and also presents pathways to engineer materials with spatially controllable structures and functionalities.

Economically Sustainable Growth of Perovskite Photovoltaics Manufacturing

Summary The significant capital expense of photovoltaics manufacturing has made it difficult for new cell and module technologies to enter the market. We present two technoeconomic models that analyze the sustainable growth of perovskite manufacturing for an R2R single-junction technology and a perovskite-silicon tandem module, focusing on the impacts of economies of scale and average selling price on profitability. We establish a cost range of $3.30/W to $0.53/W for flexible modules manufactured in factory sizes ranging from 0.3 MW/year to 1 GW/year. In addition, we model the cost to manufacture a tandem module consisting of a single-junction perovskite cell stacked in 4-terminal configuration onto a silicon cell and show how an existing manufacturer can grow at a faster rate by co-investing in tandems. Our analyses highlight potential routes to market for perovskite photovoltaics and the possibility to sustainably grow a photovoltaics manufacturing company even in markets with higher labor rates.

Block Iodide, Save Perovskite Modules

Stability of small area perovskite solar cells has been notably improved, but large area modules have not been proven stable. Recently in Joule, E. Bi and coworkers present a highly stable perovskite module that kept 90% of its initial efficiency after 1,000 h operation under illumination. The secret is an iodide diffusion blocking layer (DBL) added at the module interconnection. The DBL with 2D graphitic carbon nitride (g-C3N4) flakes can suppress iodide diffusion at the interconnection and prevent electrode corrosion.

(Invited) In Situ x-Ray Diffraction during Processing Under Extreme Conditions

Many materials are processed under extreme conditions to lock in desirable structural properties, such as metastable phases, appropriate morphologies, and defect concentrations, since these can result in wanted functionalities. Examples include splat cooling, rapid thermal processing (RTP), selective laser melting (SLM), and roll-to-roll (R2R) printing. Often the evolution of the crystalline phases that form during such extreme processing conditions are not known, and can take place through unexpected sequences, including the formation of metastable phases. Understating these phase sequences is important, since this can guide more optimal synthesis or reaction pathways, but can be challenging due to the extreme environments. We have developed X-ray diffraction and imaging approaches to following such phase and microstructure sequences in environments such as RTP (1,2,3), SLM (4,5), R2R printing (6) and hydrothermal growth (7). In this talk, I will describe our methodologies for these types of experiments and give examples of RTP used to form silver electrical contacts to silicon solar cells, hydrothermal growth of Mn-oxides and SLM of Ti-alloys. D. Fields, Md.I. Ahmad, V.L. Pool, J. Yu, D.G. Van Campen, P.A. Parilla, M.F. Toney, M.F.A.M. van Hest, Nature Comm. 7, 11143 (2016).VL Pool, B. Dou, DG Van Campen, TR Klein, FS Barnes, SE Shaheen, Md. I. Ahmad, M.F.A.M. van Hest, MF Toney, Nature Comms 8, 14075 (2017).I. Ahmad, D.G. Van Campen, J.D. Fields, J. Yu, V.L. Pool, P.A. Parilla, D.S. Ginley, M.F.A.M. Van Hest, M.F. Toney, Rev. Sci. Instrum. 86, 013902 (2015).P. Calta, J. Wang, A.M. Kiss, A.A. Martin, P.J. Depond, G.M. Guss, V. Thampy, A.Y. Fong, J. Nelson Weker, K.H. Stone, C.J. Tassone, M.J. Kramer, M.F. Toney, A. Van Buuren, M.J. Matthews, Rev. Sci. Instrum. 89, 055101 (2018).“Dynamics of pore formation during laser powder bed fusion additive manufacturing”, A Martin, N Calta, S Khairallah, J Wang, P DePond, A Fong, V Thampy, G Guss, A Kiss, KH Stone, CJ Tassone, J Weker, MF Toney, T van Buuren, M Matthews, Nature Comms, in press.X Gu, L Shaw, K Gu, MF Toney, Z Bao, Nature Comms 9, 534 (2018).B-R Chen, W Sun, D.A. Kitchaev, J.S. Mangum, V. Thampy, L.M. Garten, D.S. Ginley, B.P. Gorman, K.H. Stone, G. Ceder, M.F. Toney, LT Schelhas, Nature Comms 9, 2553 (2018).

Errata.

The October 10, 2018, article by ten Broeke et al entitled Cancer Risks for PMS2-Associated Lynch Syndrome (J Clin Oncol 10.1200/JCO.2018.78.4777) was published with an error. van Hest should have been included in the author list, between Heather Hampel and John Hopper. The following should have appeared in the list of affiliations: Liselotte van Hest, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Under AUTHOR CONTRIBUTIONS, van Hest should have been included in the section entitled Collection and assembly of data. In the section AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST, the following should have appeared: Liselotte van Hest No relationship to disclose. This has been corrected as of February 18, 2019. The authors apologize for the error.

Self-Directed in Cell Production of Methionine Analogue Azidohomoalanine by Synthetic Metabolism and Its Incorporation into Model Proteins.

Common protocols for the incorporation of noncanonical amino acids (ncAAs) into proteins require addition of the desired ncAA to the growth medium, its cellular uptake, and subsequent intracellular accumulation. This feeding scheme is generally suitable for small-scaleproof-of-concept incorporation experiments. However, it is no general solution for orthogonal translation of ncAAs, as their chemical synthesis is generally tedious and expensive. Here, we describe a simple protocol that efficiently couples in situ semi-synthetic biosynthesis of L-azidohomoalanine and its incorporation into proteins at L-methionine (Met) positions. In our metabolically engineered Met-auxotrophic Escherichia coli strain, Aha is biosynthesized from externally added sodium azide and O-acetyl-L-homoserine as inexpensive precursors. This represents an efficient platform for expression of azide-containing proteins suitable for site-selective bioorthogonal strategies aimed at noninvasive protein modifications (Tornøe et al., J Org Chem 67:3057-3064, 2002; Kiick et al., Angew Chem Int Ed 39:2148-2152, 2000; Budisa, Angew Chem Int Ed Engl 47:6426-6463, 2004; van Hest, J Am Chem Soc 122:1282-1288, 2000).

Editorial.

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTEditorialJan van Hest, Erin B. Lavik, Bradley D. Smith, Gang Zheng, and Vincent M. RotelloCite this: Bioconjugate Chem. 2015, 26, 2, 163–165Publication Date (Web):January 15, 2015Publication History Published online15 January 2015Published inissue 18 February 2015https://doi.org/10.1021/acs.bioconjchem.5b00002Copyright © 2015 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views707Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (3 MB) Get e-AlertsSUBJECTS:Biomaterials,Cancer therapy,Chemical biology,Molecular imaging,Polymers Get e-Alerts

Inside Back Cover: Polymersome Colloidosomes for Enzyme Catalysis in a Biphasic System (Angew. Chem. Int. Ed. 43/2012)

A Pickering emulsion that is stabilized by fully packed crosslinked polymersomes at the water/oil interface was prepared and applied in a biphasic enzymatic reaction. In their Communication on page 10746 ff., J. C. M. van Hest et al. show that the catalytic performance and recyclability of the Pickering emulsion is highly enhanced, when a model enzyme (CalB, red ribbon structure) is loaded either in the water phase or in the lumen of the polymersomes.

Strong in Biomaterials and Polymer Science

What was most interesting and important to our reader in 2010? Among the 270 articles published in the last two years the topics drug and gene delivery and tissue engineering could assemble the most citations in 2010, followed by more classical polymer topics such as biodegradable polymers, glycol- and biopolymers (Table 1). It's thus fair to say: Macromolecular Bioscience is strong in biomaterials and polymer science. What was most interesting to me? I have to admit that I was deeply impressed by the outstanding topical issues we published within the last year. In November, a special issue on “Instructive Materials for Functional Tissue Engineering” guest-edited by Anita Driessen-Mol, Carlijn V. C. Bouten, and Frank P. T. Baaijens (Eindhoven University of Technology, The Netherlands) highlighted topics such as cardiac repair, heart valves and blood vessel replacements, and in situ bone formation, just to name a few. Issue 9 was dedicated to “Polymers in Biomedicine” (guest-edited by Andreas Lendlein, GKSS Research Center Teltow, Germany). With the help of board member Jan C.M. van Hest (Radboud University Nijmegen, The Netherlands) we published an impressive issues on “Micro- and Nanocapsules for Biological and Biomedical Applications”. The renaissance of “Analytical Ultracentrifugation”, a topical issue organized by one of our newer board members, Helmut Cölfen (University of Konstanz, Germany) on the occasion of the 125th birthday of Theodor Svedberg, concentrated on a less classical, though not less interesting topic for Macromolecular Bioscience. All in all, the anniversary year of Macromolecular Bioscience was a year of great topical diversity, which has made it so exciting for me. A year of celebrations? Not only. It was also a year of hard work. Dealing with roughly 10% more submissions as compared to 2009, we were still able to reduce the average time to initial decision of all published articles to 35 days. But there is even more to be happy about. The number of article accesses (full-text downloads) and the number of total citations both increased by more than 20%. After one decade, Macromolecular Bioscience confirms its position among the top 5 biomaterials and the top 10 polymer journals with an ISI impact factor of 3.108. Finally, we welcome two new members to our international advisory board: We are looking forward to an intensified cooperation with Helmut Schlaad (MPI of Colloids and Interfaces, Golm, Germany) and Brent Sumerlin (Southern Methodist University, Dallas, USA). Not only our board members, but also our critical reviewers, our authors, and last but not least our readers contribute to the success of Macromolecular Bioscience. It's time to thank all of you for your commitment and your ongoing interest in our journal. Together, we are looking forward to the exciting second decade of Macromolecular Bioscience.

Pharmacokinetics of mycophenolic acid in severe lupus nephritis

Mycophenolic acid (MPA) is an effective treatment for active lupus nephritis despite its variable efficacy in different ethnic groups. Here we tested whether pharmacokinetic monitoring may help to optimize dosing of MPA in an Asian population. Patients with biopsy-proven class III or IV lupus nephritis (ISN/RPS category) were treated with mycophenolate mofetil or enteric-coated mycophenolate sodium. One month after initiating treatment we measured plasma MPA levels in eight samples taken over a 12-h period after drug administration. The mean area under the time-dependent curve for MPA of responding patients was significantly higher than those not responding. Successful treatment was seen in patients with areas >45 mg h/l. The dosage of the drug was not related to MPA pharmacokinetics. In the mycophenolate mofetil group, however, MPA-area under the curve was positively, and significantly, correlated with trough or 1 h after dose concentrations and associated with a therapeutic response. Thus, our study shows that MPA pharmacokinetics were positively correlated with therapeutic responses of mycophenolate, suggesting that controlling the concentrations may improve its therapeutic efficacy in lupus nephritis. As the absorption and pharmacokinetic peak of enteric-coated tablets is slower, it is important to take different formulations into account when determining optimal MPA concentrations.

Happy Birthday, MBS!

Happy Birthday, MBS!

Identification and Quantitation of Newly Synthesized Proteins in Escherichia coli by Enrichment of Azidohomoalanine-labeled Peptides with Diagonal Chromatography

A method is presented to identify and quantify several hundreds of newly synthesized proteins in Escherichia coli upon pulse labeling cells with the methionine analogue azidohomoalanine (azhal). For the first 30 min after inoculation, a methionine-auxotrophic strain grows equally well on azhal as on methionine. Upon a pulse of 15 min and digestion of total protein, azhal-labeled peptides are isolated by a retention time shift between two reversed phase chromatographic runs. The retention time shift is induced by a reaction selective for the azido group in labeled peptides using tris(2-carboxyethyl)phosphine. Selectively modified peptides are identified by reversed phase liquid chromatography and on-line tandem mass spectrometry. We identified 527 proteins representative of all major Gene Ontology categories. Comparing the relative amounts of 344 proteins synthesized in 15 min upon a switch of growth temperature from 37 to 44 degrees C showed that nearly 20% increased or decreased more than 2-fold. Among the most up-regulated proteins many were chaperones and proteases in accordance with the cells response to unfolded proteins due to heat stress. Comparison of our data with results from previous microarray experiments revealed the importance of regulation of gene expression at the level of transcription of the most elevated proteins under heat shock conditions and enabled identification of several candidate genes whose expression may predominantly be regulated at the level of translation. This work demonstrates for the first time the use of a bioorthogonal amino acid for proteome-wide detection of changes in the amounts of proteins synthesized during a brief period upon variations in cellular growth conditions. Comparison of such data with relative mRNA levels enables assessment of the separate contributions of transcription and translation to the regulation of gene expression.

Vascular anomalies

Vascular anomalies

Synthesis and assembly behavior of nucleobase‐functionalized block copolymers

The use of oligonucleobase moieties in materials science has experienced growing interest in recent years. Several researchers have elegantly shown the application of oligonucleotides as versatile building blocks for the synthesis of, for example, controlled nanoscaled structures and molecular machines. Also, in polymer science, oligonucleobases have become a topic of investigation. Nucleobase-functionalized polymers have been applied in various applications such as template polymerizations and supramolecular materials, in which the noncovalent anchors are based on oligonucleotides. Lutz et al. found that the incorporation of a complementary nucleobase functionality into synthetic copolymers leads to materials that can exhibit a DNAlike melting behavior. In addition, Rowan and coworkers prepared thermoresponsive supramolecular polymer materials, in which the noncovalent interactions are based on single nucleobase moieties. Recent advances in controlled (radical) polymerization techniques such as atom transfer radical polymerization (ATRP) have further increased activity in the polymer chemistry field. These methods allow the formation of well-defined polymer architectures in which a large variety of biological functionalities, such as nucleobases, can be included. It is well known that amphiphilic block copolymers have the ability to assemble into multiple morphologies in solution. Depending on a number of parameters, such as the ratio of the hydrophilic and hydrophobic blocks, the morphology can vary from spherical micelles, rods, and vesicles to large compound micelles (LCMs). Even more structural control is possible when block copolymers are used that are built up out of a synthetic part and a biomolecular part. Another method was developed by Rotello and coworkers, who prepared plug and play polymers that facilitated recognition through hydrogen-bonding interactions to change the morphology of the polymers or even direct self-assembly of patterned surfaces. Several examples in which peptide sequences are incorporated into polymer chains have been shown to control the material properties and enable self-assembly into well-defined nanoscale architectures. Besides proteins, this could also apply to nucleobase block copolymers. In previous investigations, it already has been demonstrated that the incorporation of small oligonucleotide strands has vast potential to influence the aggregation of block copolymers. Often the incorporation of these biofunctional moieties into the polymer chain facilitates some form of aggregation. Either the aggregation of the biological functionality is enhanced by the polymer chain or aggregation of the polymer chains is increased via specific interactions between the biological functionalities. In addition, the nanocompartmentalization by block copolyCorrespondence to: J. C. M. van Hest (E-mail: j.vanhest@ science.ru.nl)

Some aspects of repair in native and non-native speaker conversations in English

Abstract The ability to carry out repairs is a key skill in spoken discourse for non-native speakers of English and has been widely studied. However, VAN HEST et al. (1997) have suggested that investigations into repair in L2 need to be more theoretically driven and less concerned with individual differences. Drawing on information from a pilot study of twenty-three conversations, lasting 185 minutes between six native and six non-native speakers, this paper argues that there is no conflict between a concern with individual differences and theory building. What is needed is a contextualised theory which is grounded in particular situations and individual differences. The paper identifies three possible areas of difficulty that may arise if a theory is not contextualised. Firstly, the paper argues that theory driven research encourages methods of data collection that we characterise as experimental and suggest that these need to be supplemented by more naturalistic forms of data collection. Secondly, the paper criticises the view that there are general preferences as to who initiates and who completes repairs and argues that a contextualised theory of repair would capture initiation/completion patterns more adequately. Finally, the paper argues that the distinction between native and non-native speakers needs to be re-examined. This is supported by the finding in the pilot study that there was little variation between native and non-native speakers in terms of these analyses.